Overview

Also Known As:nNOS KO

nNos KO mice may useful when studying structure and function of neurons and their synaptic connections in the brain and periphery.

Donating Investigator

IMR Colony, The Jackson Laboratory

Genetic overview

Genetic Background	Generation
000664 C57BL/6J	N11p+N3F11 (2019-12-31 00:00:00)

Nos1^tm1Plh

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Nos1	nitric oxide synthase 1, neuronal

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Research Applications

Diabetes and Obesity Research
Neurobiology Research

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Base Price

Starting at:

$278.00 Domestic price for female 4-week

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Details

Important Note

The mice of this strain have been backcrossed more than 10 backcrosses to C57BL/6J, making this strain more effective for studies of the Nos1 KO than the incipient stock (#002633).

Detailed Description

The nitric oxide signaling molecule produced by the neuronal Nos1 gene is widely expressed, affecting diverse systems. The knockout of this gene has been shown to affect such normal functions as cognition and behavior, long-term memory, cortical development, colonic motility, skeletal muscle contractility, ovarian cycle regulation, cardiac/cardiovascular function, and certain immune system responses. Western blots of brain homogenates from homozygous mutant mice showed no detectable protein. However, splice variants are expressed and variable low levels of NOS activity are seen in the brain.

Heterozygous mice are viable and fertile, while some lethality is seen in homozygotes due to stomach hypertrophy. The first publication describing this knock-out reported that mutants have enlarged stomachs with hypertrophy of the pyloric sphincter and the circular muscle layer (Huang et al., 1993). Male homozygotes of this strain were initially reported to be more aggressive than control mice, but this has been since attributed to heterogeneity of the stock before it was sufficiently backcrossed to the C57BL/6J genetic background. The C57BL/6J-congenic strain at The Jackson Laboratory (Stock No. 002986) shows normal behavior in this regard.

The Jackson Laboratory preferred mating scheme for Stock No. 002986 is breeding heterozygous mice together, or by breeding heterozygous females to homozygous males. Breeding heterozygous mice together results in less than Mendelian ratios of homozygous pups. Of note, we attempted breeding homozygotes together and found they generated offspring at a much slower rate.

In an attempt to offer alleles on well-characterized or multiple genetic backgrounds, alleles are frequently moved to a genetic background different from that on which an allele was first characterized. This is the case for this strain. It should be noted that the phenotype could vary from that originally described. We will modify the strain description if necessary as published results become available.

Development

A targeting vector was designed to replace exon 1 of the nitric oxide synthase 1, neuronal (Nos1) gene with a neomycin cassette. This exon encodes the initiation site and amino acids 1 - 159 of the protein. The targeting vector was electroporated into 129S4/SvJae
-derived Jl ES cells that were injected into C57BL/6 blastocysts. Injected blastocysts were implanted in (C57BL/6 x DBA/2)Fl mice. Chimeric progeny were backcrossed to C57BL/6 mice. Some mice were further backcrossed to C57BL/6J mice (Stock No. 000664) for more than 10 generations to produce this Stock No. 002986.

Control Suggestions

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Huang PL; Dawson TM; Bredt DS; Snyder SH; Fishman MC. 1993. Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75(7):1273-86PubMed: 7505721 MGI: J:16390

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Genetics

Nos1^tm1Plh

Allele Symbol: Nos1^tm1Plh

Allele Name	targeted mutation 1, Paul L Huang
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	alphaNOS1; Kn; N2KO; nNOS-; nNOS KO; nNOS^-; NOS^delta
Gene Symbol and Name	Nos1, nitric oxide synthase 1, neuronal
Gene Synonym(s)
Strain of Origin	129S4/SvJae
Chromosome	5
Molecular Note	A neomycin cassette replaced exon 1. This exon encodes the initiation site and amino acids 1 - 159 of the protein. Northern blots of brain homogenates from homozygous mutant mice showed no detectable mRNA. Western blots of brain homogenates from homozygous mutant mice showed no detectable protein. However, splice variants are expressed and variable low levels of NOS activity are seen in the brain.
Mutations Made By	Dr. Paul Huang, Mass General Hospital, Harvard Med Sch

Disease/Phenotype

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

hypertrophic pyloric stenosis

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Nos1^tm1Plh related

Diabetes and Obesity Research
- Insulin Resistance
Neurobiology Research
- Neurotransmitter Receptor and Synaptic Vesicle Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae * C57BL/6

behavior/neurological phenotype

abnormal mating frequency
- by 7 to 8 h after introduction of a female, the number of mounts made by males is 2 to 3 times greater compared to wild-type males
- the number of mounts fails to decrease significantly 1 h after the introduction of an anestrus female to the cage
- when placed with females in estrus males display excessive and inappropriate mounting

increased aggression towards females
- when placed with females in estrus males display excessive and inappropriate mounting

increased aggression towards males
- for males latency to first attack is reduced to about 1/5 that of wild-type mice
- for males the duration of aggressive encounters is increased
- in a resident intruder assay males display more aggressive encounters and initiate more of the aggressive encounters compared to wild-type mice
- male mice display submissive postures about 1/10 as frequently as wild-type controls
- Normal - no increase in aggression is seen in females

cardiovascular system phenotype

abnormal cardiac muscle relaxation
- time to 50% relaxation is increased

decreased cardiac muscle contractility
- attenuation of the beta-adrenergic inotropic responses indicating a decrease in myocardial contractile reserve

heart left ventricle hypertrophy
- age related

increased ventricle muscle contractility
- isolated ventricular myocytes display greater overall shortening at all stimulation frequencies between 0.2 and 10 Hz
- shortening in response to beta-adrenergic stimulation is greatly enhanced

cellular phenotype

abnormal mitochondrial physiology
- despite similar ratios of mitochondrial to nuclear DNA the amount of citrate synthase is significantly increased in homogenates from the heart, kidney and liver

digestive/alimentary phenotype

abnormal stomach wall morphology
- hypertrophy of the pyloric sphincter and the circular muscle layer
- with age, the stomachs lose their interior folds and undergo thinning of the walls, however the intestine appears normal

enlarged stomach
- stomach dilation, however architecture of the stomach layers is preserved

pyloric sphincter hypertrophy

pyloric stenosis

stomach smooth muscle circular layer hypertrophy

growth/size/body region phenotype

heart left ventricle hypertrophy
- age related

homeostasis/metabolism phenotype

abnormal carbon dioxide production
- in awake mice carbon dioxide production is significantly decreased during 12% oxygen compared to 100% oxygen in mutant but not in wild-type mice

abnormal oxygen consumption
- in awake mice the magnitude of the decrease in oxygen consumption under 21% or 12% oxygen is greater than that in wild-type controls

increased oxygen consumption

increased physiological sensitivity to xenobiotic
- sodium cyanide induced respiratory stimulation is increased in mutants compared to wild-type mice

liver/biliary system phenotype

abnormal hepatocyte morphology
- fat droplets are absent from the cytosol of hepatocytes

abnormal liver morphology
- lipid content of the liver is increased
- unlike in wild-type livers, glycogen content is increased in zone 3 relative to zone 1 of the liver

mammalian phenotype

growth/size/body region phenotype
- Normal - no difference in body weight is detected at 1 year of age

homeostasis/metabolism phenotype
- Normal - despite the increase in aggressive and sexual behaviors, no significant difference is detected in blood testosterone levels compared to wild-type males

nervous system phenotype
- Normal - homozygous mice do not exhibit defects in brain structure or neuron degeneration

mortality/aging

decreased sensitivity to induced morbidity/mortality
- in anesthetized mice under 12% oxygen all mutant mice survived while 4 of 14 wild-type mice died

decreased survivor rate
- survival at 20 months is reduced compared to Nos3 null mice

premature death
- slight increase in premature death
- survival at 20 months is reduced compared to Nos3 null mice
- the relative risk of death by 20 months of age is 2.5 times higher than in Nos3 null mice

muscle phenotype

abnormal cardiac muscle relaxation
- time to 50% relaxation is increased

abnormal muscle physiology
- muscle atrophy induced by transection of the sciatic nerve in the right hindlimb is reduced

decreased cardiac muscle contractility
- attenuation of the beta-adrenergic inotropic responses indicating a decrease in myocardial contractile reserve

heart left ventricle hypertrophy
- age related

increased ventricle muscle contractility
- isolated ventricular myocytes display greater overall shortening at all stimulation frequencies between 0.2 and 10 Hz
- shortening in response to beta-adrenergic stimulation is greatly enhanced

pyloric sphincter hypertrophy

stomach smooth muscle circular layer hypertrophy

nervous system phenotype

abnormal brain morphology
- electron microscopy analysis indicates a lower density of mitochondria in the cortex of the brain
- Normal - however, the ratio of mitochondrial to nuclear DNA is similar to controls

abnormal dendrite morphology
- decrease in the number of branches is first detected at about 100 um from the cell body with a peak in the decrease between about 160 - 260 um
- difference in branch number is limited to third and fourth order branches
- Normal - however, the number of primary dendrites and the longest dendritic path from a cell are not different from wild-type controls
- motor neurons display a significant decrease in the number of dendritic branches

abnormal motor neuron morphology
- Normal - however, the number of primary dendrites, the longest dendritic path from a cell, and cell body size are not different from wild-type controls
- motor neurons display a significant decrease in the number of dendritic branches

abnormal nervous system physiology
- delay in Wallerian degeneration following transection of the sciatic nerve in the right hindlimb

abnormal peripheral nervous system regeneration
- following transection of the sciatic nerve in the right hindlimb time to recovery of motor function is delayed
- following transection of the sciatic nerve in the right hindlimb uncontrolled sprouting is increased
- Normal - however, myelination following transection is not significantly different from controls

renal/urinary system phenotype

abnormal renal tubule morphology
- electron microscopy analysis indicates a lower density of mitochondria in tubule cells of the kidney
- Normal - however, the ratio of mitochondrial to nuclear DNA is similar to controls

reproductive system phenotype

abnormal ovulation
- ovulatory efficiency (number oocytes recovered divided by the number of ovarian rupture sites) is reduced in homozygotes
- significantly fewer oocytes are recovered following gonadotropin-stimulated ovulation in homozygous mutant females compared to wild-type females

respiratory system phenotype

abnormal breathing pattern
- anesthetized mice under 21% or 12% oxygen show period increases in respiratory rate not seen in wild-type mice

abnormal pulmonary respiratory rate response
- in awake mice, the magnitude of the decrease in respiratory rate following brief exposure to 100% oxygen was greater than that in wild-type mice

increased pulmonary respiratory rate
- anesthetized mice do not display respiratory depression under 12% oxygen, unlike wild-type controls
- in anesthetized mutant mice the increase in ventilation under 21% oxygen results from an increase in both respiratory rate and tidal phrenic activity, unlike in wild-type mice where only tidal phrenic activity is increased
- in awake and anesthetized mice the magnitude of the increases in respiratory rate at 21% and 12% oxygen are greater than in wild-type controls
- sodium cyanide induced respiratory stimulation is increased in mutants compared to wild-type mice

increased pulmonary ventilation
- in awake and anesthetized mice the magnitude of the increase in minute ventilation is greater at both 21% and 12% oxygen compared to wild-type controls
- in awake mice the significant increases are seen in minute ventilation at both 21% and 12% oxygen unlike in wild-type controls where increases are seen only at 12% oxygen

increased tidal volume
- in awake mice the magnitude of the increases in tidal volume at 21% and 12% oxygen are greater than in wild-type controls

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae

behavior/neurological phenotype

impaired balance
- mice show no improvement in their latency to fall off a pole or plank in the dark versus the light phase, unlike in wild-type controls resulting in deficits in balance compared to wild-type mice during the dark phase

digestive/alimentary phenotype

abnormal gastroesophageal sphincter physiology
- efferent vagal stimulation induced lower esophageal sphincter relaxation is significantly attenuated
- lower esophageal sphincters fail to display electrical field stimulation (60 V, 5 Hz) induced relaxation or rebound contraction
- mice show a range of responses to pharyngeal stimulation including no relaxation, partial relaxation , and sporadic near complete relaxation of the lower esophageal sphincter
- swallowing induced lower esophageal sphincter relaxation is significantly attenuated
- the mean resting lower esophageal sphincter pressure is significantly higher

cardiovascular system phenotype

abnormal blood circulation
- the increase in cerebral blood flow induced by glutamate, perioral stimulation, or harmaline is significantly attenuated

abnormal vascular wound healing
- following carotid artery ligation the extent of neointimal formation is increased and luminal narrowing is worsened compared to wild-type controls

altered response of heart to induced stress
- myocardial infarct size following 30 min of global ischemia is increased compared to controls

decreased coronary flow rate
- Normal - however, coronary flow per beat is not significantly different from controls
- in isolated perfused hearts

decreased heart weight

growth/size/body region phenotype

decreased body weight

hematopoietic system phenotype

abnormal leukocyte adhesion
- dramatic increase in baseline leukocyte adherence
- treatment with an anti-P-selectin antibody significantly reduces the adhesion response in mutant but not in wild-type mice

abnormal neutrophil physiology
- following thioglycollate injection neutrophil accumulation in the peritoneum is significantly enhanced compared to wild-type mice

enhanced leukocyte tethering or rolling
- increase in baseline rolling
- treatment with a low dose of thrombin significantly increases rolling in mutant but not in wild-type mice
- treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice

homeostasis/metabolism phenotype

abnormal vascular wound healing
- following carotid artery ligation the extent of neointimal formation is increased and luminal narrowing is worsened compared to wild-type controls

altered response of heart to induced stress
- myocardial infarct size following 30 min of global ischemia is increased compared to controls

decreased cerebral infarction size
- following occlusion of the middle cerebral artery infarct size is decreased

decreased susceptibility to injury
- 24 h after aspiration bulbectomy the number of apoptotic cells in the piriform cortex is reduced compared to similarly treated wild-type mice

decreased susceptibility to neuronal excitotoxicity
- the size of striatal lesions induced by malonate are significantly reduced compared to similarly treated controls

insulin resistance
- insulin resistance in peripheral tissues

immune system phenotype

abnormal leukocyte adhesion
- dramatic increase in baseline leukocyte adherence
- treatment with an anti-P-selectin antibody significantly reduces the adhesion response in mutant but not in wild-type mice

abnormal neutrophil physiology
- following thioglycollate injection neutrophil accumulation in the peritoneum is significantly enhanced compared to wild-type mice

enhanced leukocyte tethering or rolling
- increase in baseline rolling
- treatment with a low dose of thrombin significantly increases rolling in mutant but not in wild-type mice
- treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice

mammalian phenotype

behavior/neurological phenotype
- Normal - no defects in circadian rhythms are detected in a wheel running assay either under entrained or free running conditions
- Normal - unlike in earlier reports males show no signs of increased aggression

cardiovascular system phenotype
- Normal - unlike in mice null for Nos3 no significant abnormalities in hypoxic pulmonary vasoconstriction, vasodilation in response to bradykinin, or right ventricle systolic pressure are detected

nervous system phenotype
- Normal - despite the ability of NOS inhibitors to decrease long term potentiation, no significant decrease in long term potentiation is detected at 1 h after tetanus
- Normal - unlike cerebral blood flow, the intensity of neural activation induced by perioral stimulation is not significantly different from controls

reproductive system phenotype
- Normal - unlike in Nos3 null mice, the increase in maximal penile intracavernous pressure induced by papaverine is not significantly different from wild-type controls

vision/eye phenotype
- Normal - no defects are detected in visual acuity

mortality/aging

decreased survivor rate
- about 80% survival rate at 10 months of age

premature death
- about 20% die before 10 months of age

muscle phenotype

abnormal gastroesophageal sphincter physiology
- efferent vagal stimulation induced lower esophageal sphincter relaxation is significantly attenuated
- lower esophageal sphincters fail to display electrical field stimulation (60 V, 5 Hz) induced relaxation or rebound contraction
- mice show a range of responses to pharyngeal stimulation including no relaxation, partial relaxation , and sporadic near complete relaxation of the lower esophageal sphincter
- swallowing induced lower esophageal sphincter relaxation is significantly attenuated
- the mean resting lower esophageal sphincter pressure is significantly higher

abnormal muscle physiology
- hyperpolarization and induction of an inhibitory junction potential in response to electrical field stimulation under nonadrenergic noncholinergic conditions in jejunal muscle strips are markedly reduced
- the resting membrane potential of jejunal smooth muscle cells is depolarized about 5 mV compared to wild type cells

abnormal muscle relaxation
- lower esophageal sphincters fail to display electrical field stimulation (60 V, 5 Hz) induced relaxation or rebound contraction
- the decrease in muscle contractions in jejunal muscle strips in response to electrical field stimulation is markedly reduced

nervous system phenotype

abnormal long term potentiation
- following a theta burst protocol at a weak intensity enhancement of EPSPs during the first 3 minutes after stimulation is significantly small compared to controls
- Normal - however, no significant differences are detected when a stronger intensity stimulation is used

abnormal nervous system physiology
- 24 h after aspiration bulbectomy the number of apoptotic cells in the piriform cortex is reduced compared to similarly treated wild-type mice

absent long term depression
- addition of uncaged NO or photoreleased cGMP to the stimulation protocol also fails to induce long term depression in Purkinje cells, unlike in wild-type mice
- stimulation of parallel fibers with a 50 msec postsynaptic depolarizations fails to induce long term depression in Purkinje cells

decreased cerebral infarction size
- following occlusion of the middle cerebral artery infarct size is decreased

decreased susceptibility to neuronal excitotoxicity
- the size of striatal lesions induced by malonate are significantly reduced compared to similarly treated controls

decreased synaptic glutamate release
- glutamate release after NMDA stimulation is significantly attenuated in the cerebral cortex, partially reduced in the striatum but unaffected in the hippocampus

cellular phenotype

abnormal leukocyte adhesion
- dramatic increase in baseline leukocyte adherence
- treatment with an anti-P-selectin antibody significantly reduces the adhesion response in mutant but not in wild-type mice

decreased susceptibility to neuronal excitotoxicity
- the size of striatal lesions induced by malonate are significantly reduced compared to similarly treated controls

enhanced leukocyte tethering or rolling
- increase in baseline rolling
- treatment with a low dose of thrombin significantly increases rolling in mutant but not in wild-type mice
- treatment with an anti-P-selectin antibody significantly reduces the rolling response in mutant but not in wild-type mice

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae * C57BL/6J

behavior/neurological phenotype

abnormal behavioral response to addictive substance
- following dosing with 2.5 or 4.5 gm/kg mice regain their righting reflex faster compared to similarly treated wild-type controls

abnormal liquid preference
- Normal - however, the concentration dependent aversion to quinine is not significantly different from controls
- the concentration dependent increase in sucrose preference is more pronounced in mutants compared to wild-type controls

abnormal spatial learning
- Normal - however, performance in the less stressful multiple T maze is improved compared to controls
- impaired performance during memory recall trials in a Morris water maze

enhanced behavioral response to addictive substance
- mice fail to develop tolerance to alcohol induced hypothermia following multiple ethanol injection

enhanced coordination
- in the last trial mice spend more time on the rotarod compared to wild-type controls

increased aggression towards males
- Background Sensitivity - mice display increased aggression compared to C57BL/6J mice but not compared to 129S2/SvPas mice
- Background Sensitivity - unlike mice on a congenic C57BL/6J background, male mice display increased aggression

increased alcohol consumption
- Normal - however, when presented with dilute solutions of alcohol (2 - 4%), alcohol consumption does not differ from controls
- mice consume more alcohol when presented with solutions containing high concentrations of alcohol (greater than 8% alcohol) compared to wild-type controls

increased anxiety-related response
- increase in grooming behavior is seen in mice in an open field and during an elevated plus maze assay suggesting an increase in the amount of stress mice experience under these conditions

increased coping response
- in a forced swim test mice spend more time actively swimming and less time immobile compared to wild-type controls

increased grooming behavior
- seen in mice in an open field and during an elevated plus maze assay suggesting an increase in the amount of stress mice experience under these conditions

cardiovascular system phenotype

decreased mean systemic arterial blood pressure

increased heart rate
- atria display higher baseline heart rates
- decrease in heart rate in response to vagal nerve stimulation is slower

digestive/alimentary phenotype

abnormal digestion
- stomachs often contain bezoars even after 2 days of fasting

enlarged duodenum
- diffuse enlargement

enlarged esophagus
- diffuse enlargement

enlarged stomach
- diffuse enlargement
- weight and volume are increased

gastric hypertrophy
- muscular thickening is seen throughout the stomach

impaired gastric peristalsis
- gastric emptying of solids and liquids is delayed

pyloric sphincter hypertrophy
- pyloric sphincter thickness is increased by 17% compared to controls

growth/size/body region phenotype

enlarged esophagus
- diffuse enlargement

homeostasis/metabolism phenotype

abnormal renal water reabsorption
- the rate of net fluid absorption is reduced in the proximal tubules

increased urine bicarbonate level
- increase in urine bicarbonate concentration

increased urine pH
- increase in urine pH

metabolic acidosis
- arterial blood pH and bicarbonate concentrations are reduced resulting in a modest but significant metabolic acidosis

mammalian phenotype

digestive/alimentary phenotype
- Normal - unlike in human patients with Infantile Hypertrophic Pyloric Stenosis, the luminal aperture of the pyloric sphincter is not significantly smaller in relaxed tissues compared to wild type controls

homeostasis/metabolism phenotype
- Normal - despite differences in behavioral responses to alcohol, no differences in blood alcohol elimination are detected

muscle phenotype

pyloric sphincter hypertrophy
- pyloric sphincter thickness is increased by 17% compared to controls

renal/urinary system phenotype

abnormal renal reabsorption
- the rate of bicarbonate absorption is reduced in the proximal tubules

abnormal renal water reabsorption
- the rate of net fluid absorption is reduced in the proximal tubules

increased urine bicarbonate level
- increase in urine bicarbonate concentration

increased urine pH
- increase in urine pH

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae * C57BL/10ScSn

mammalian phenotype

muscle phenotype
- Normal - no abnormalities in muscle morphology are detected

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
B6;129S4-Nos1/J

behavior/neurological phenotype

abnormal sleep pattern
- Normal - however, there is no significant difference in the amount of time spent in non-REM sleep and mice display normal diurnal variation in sleep patterns
- mice spend less time in REM sleep as a result of fewer REM episodes and lengthened duration of the inter REM intervals

cellular phenotype

abnormal osteoclast differentiation
- in culture RANKL and M-CSF induced osteoclast formation are increased

hematopoietic system phenotype

abnormal osteoclast differentiation
- in culture RANKL and M-CSF induced osteoclast formation are increased

immune system phenotype

abnormal osteoclast differentiation
- in culture RANKL and M-CSF induced osteoclast formation are increased

mammalian phenotype

behavior/neurological phenotype
- Normal - increased aggressive behavior is not seen in males unlike in other reports

nervous system phenotype

abnormal brain wave pattern
- during non-REM sleep the absolute value of slow wave activity is increased

skeleton phenotype

abnormal osteoclast differentiation
- in culture RANKL and M-CSF induced osteoclast formation are increased

abnormal skeleton development
- indices of bone formation and resorption are lower

abnormal trabecular bone morphology
- trabecular bone tends to extend deeper into the metaphysis

increased bone mineral content
- bone mineral content is increased

increased bone mineral density
- bone mineral density is increased

increased trabecular bone thickness

increased trabecular bone volume

The following phenotype relates to a compound genotype created using this strain

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
B6.129S4-Nos1

behavior/neurological phenotype

abnormal maternal behavior
- about a 90% decrease in the amount of time lactating females spend actively attacking or biting an intruder male
- Normal - in contrast to the decrease in maternal aggression, no defect in pup retrieval is detected
- lactating females display decreased aggression towards intruder males

abnormal seizure response to inducing agent
- when exposed to hyperbaric oxygen (greater than 99% oxygen) at 5 ATA for 60 min the time to first seizure in freely moving mice is significantly longer compared to similarly treated wild-type mice

decreased aggression towards males
- about a 90% decrease in the amount of time lactating females spend actively attacking or biting an intruder male
- lactating females display decreased aggression towards intruder males

increased aggression towards males
- increase in the number and duration of attacks and decrease in the latency to attack in a resident intruder assay
- significantly higher concentrations of serotonin receptor agonists are required to reduce aggressive behavior than in wild-type controls
- treatment with a serotonin precursor dramatically reduces aggressive behavior

cardiovascular system phenotype

abnormal blood-brain barrier function
- kainic acid injection of hippocampi does not cause blood-brain barrier breakdown

decreased susceptibility to induced choroidal neovascularization
- knockouts show a 58% decrease in neovascularization at sites of laser-induced Bruch's membrane rupture compared to heterozygous littermates

cellular phenotype

decreased susceptibility to neuronal excitotoxicity
- kainic acid does not cause the hippocampal neurons to degenerate

maternal effect
- pups of homozygous females weigh more than pups of wild-type females

homeostasis/metabolism phenotype

abnormal serotonin level
- as no change is seen on the concentration of the serotonin metabolite, 5-HIAA, the 5-HIAA to serotonin (5-HT) ratio is reduced in the cortex, hypothalamus, midbrain, and cerebellum indicating a decrease in serotonin turnover
- total serotonin content is increased in the cerebral cortex, hypothalamus, hippocampus, midbrain and cerebellum

decreased adiponectin level

decreased cerebral infarction size
- however, infarct size is increased compared to mice hemizygous for Tg(SOD1)76Dpr
- infarction sized induced by middle cerebral artery obstruction is reduced in males, but not in females, compared to wild-type controls

decreased susceptibility to ischemic brain injury
- functional deficits following middle cerebral artery obstruction are reduced compared to wild-type controls

decreased susceptibility to neuronal excitotoxicity
- kainic acid does not cause the hippocampal neurons to degenerate

increased circulating triglyceride level
- elevated plasma triglycerides

mammalian phenotype

behavior/neurological phenotype
- Background Sensitivity - unlike mice on a mixed 129S4/SvJae and C57BL/6J background, congenic male mice do not display significantly increased aggression compared to wild-type controls

cardiovascular system phenotype
- Normal - unlike mice null for Nos3, ischemia induced retinal neovascularization is not significantly different from controls

nervous system phenotype

abnormal blood-brain barrier function
- kainic acid injection of hippocampi does not cause blood-brain barrier breakdown

abnormal nervous system physiology
- in anesthetized mice the latency to hyperbaric oxygen (greater than 99% oxygen) at 5 ATA induced EEG seizure is increased compared to similarly treated wild-type mice
- striatal accumulation of 3-nitrotyrosine during hyperbaric oxygen exposure is decreased compared to similarly treated wild-type mice

abnormal seizure response to inducing agent
- when exposed to hyperbaric oxygen (greater than 99% oxygen) at 5 ATA for 60 min the time to first seizure in freely moving mice is significantly longer compared to similarly treated wild-type mice

abnormal serotonin level
- as no change is seen on the concentration of the serotonin metabolite, 5-HIAA, the 5-HIAA to serotonin (5-HT) ratio is reduced in the cortex, hypothalamus, midbrain, and cerebellum indicating a decrease in serotonin turnover
- total serotonin content is increased in the cerebral cortex, hypothalamus, hippocampus, midbrain and cerebellum

decreased cerebral infarction size
- however, infarct size is increased compared to mice hemizygous for Tg(SOD1)76Dpr
- infarction sized induced by middle cerebral artery obstruction is reduced in males, but not in females, compared to wild-type controls

decreased susceptibility to ischemic brain injury
- functional deficits following middle cerebral artery obstruction are reduced compared to wild-type controls

decreased susceptibility to neuronal excitotoxicity
- kainic acid does not cause the hippocampal neurons to degenerate

vision/eye phenotype

decreased susceptibility to induced choroidal neovascularization
- knockouts show a 58% decrease in neovascularization at sites of laser-induced Bruch's membrane rupture compared to heterozygous littermates

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
B6.129S4-Nos1/J

growth/size/body region phenotype

decreased body weight
- in males only

immune system phenotype

decreased inflammatory response
- fever in response to LPS injection is partially reduced compared to wild-type controls
- Normal - however, fever in response to turpentine injection is not different from controls
- reduction in fever response mainly occurs during the early phase of fever response

muscle phenotype

decreased skeletal muscle weight
- decrease in skeletal muscle weight in males

impaired skeletal muscle contractility
- decrease in the maximal tetanic force generating capacity of the tibialis anterior muscle in males
- Normal - however, when normalized to muscle size the force generating capacity is not significantly different from wild-type controls
- peak twitch force is decreased in the tibialis anterior muscle of male mice

muscle fatigue
- tibialis anterior muscle displays an increase in the susceptibility to contraction induced fatigue in both males and females

Genotype: Nos1^tm1Plh/Nos1⁺
B6.129S4-Nos1

cardiovascular system phenotype

abnormal cardiovascular system physiology
- exercise training fails to augment the phenylephrine induced pulse interval response

abnormal heart rate
- exercise training fails to augment the phenylephrine induced or vagal nerve stimulation bradycardia responses
- Normal - no differences in heart rate responses are detected in the absence of exercise training

homeostasis/metabolism phenotype

abnormal physiological response to xenobiotic
- exercise training fails to augment the phenylephrine induced bradycardia and pulse interval responses
- Normal - no differences in phenylephrine induced responses are seen in untrained mice

References

Huang PL; Dawson TM; Bredt DS; Snyder SH; Fishman MC. 1993. Targeted disruption of the neuronal nitric oxide synthase gene. Cell 75(7):1273-86PubMed: 7505721 MGI: J:16390

Additional References

Barouch LA; Harrison RW; Skaf MW; Rosas GO; Cappola TP; Kobeissi ZA; Hobai IA; Lemmon CA; Burnett AL; O'Rourke B; Rodriguez ER; Huang PL; Lima JA; Berkowitz DE; Hare JM. 2002. Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoforms. Nature 416(6878):337-9PubMed: 11907582 MGI: J:75645
de Jonge WJ; Hallemeesch MM; Kwikkers KL; Ruijter JM; de Gier-de Vries C; van Roon MA; Meijer AJ; Marescau B; de Deyn PP; Deutz NE; Lamers WH. 2002. Overexpression of arginase I in enterocytes of transgenic mice elicits a selective arginine deficiency and affects skin, muscle, and lymphoid development. Am J Clin Nutr 76(1):128-40PubMed: 12081826 MGI: J:80556
Shankar RR; Wu Y; Shen HQ; Zhu JS; Baron AD. 2000. Mice with gene disruption of both endothelial and neuronal nitric oxide synthase exhibit insulin resistance. Diabetes 49(5):684-7PubMed: 10905473 MGI: J:62229
Tao F; Tao YX; Zhao C; Dore S; Liaw WJ; Raja SN; Johns RA. 2004. Differential roles of neuronal and endothelial nitric oxide synthases during carrageenan-induced inflammatory hyperalgesia. Neuroscience 128(2):421-30PubMed: 15350652 MGI: J:93612

Additional - Nos1^tm1Plh related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Standard PCR:Nos1
- Separated PCR:Nos1 Alternate2
- Probe:Nos1 Probe
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

The Jackson Laboratory preferred mating scheme for Stock No. 002986 is breeding heterozygous mice together, or by breeding heterozygous females to homozygous males. Breeding heterozygous mice together results in less than Mendelian ratios of homozygous pups.
Of note, we attempted breeding homozygotes together and found they generated offspring at a much slower rate.
Some lethality related to stomach hypertrophy observed in homozygotes.
- Additional Breeding and Husbandry Support
Mating System
- Heterozygote x Heterozygote
- Heterozygote x Homozygote
Appearance
- black
  Related Genotype: a/a
Citation
When using the nNOS KO mouse strain in a publication, please cite the originating article(s) and include JAX stock #002986 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX10 (Standard)

Pricing & Availability

Available

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or Wild-type for Nos1<tm1Plh>

Payment Terms and Conditions

Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

Phone: 207-288-6470

Email: TechTran@jax.org

JAX® Mice, Products & Services Conditions of Use

"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCT(S)" means biological materials supplied by JACKSON, and their derivatives. "SERVICES" means projects conducted by JACKSON for other parties that may include but are not limited to the use of MICE or PRODUCTS. "RECIPIENT" means each recipient of MICE, PRODUCTS, or SERVICES provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than internal research, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services. Acceptance of MICE, PRODUCTS or SERVICES from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON’s prior written authorization.

No Warranty

MICE, PRODUCTS AND SERVICES ARE PROVIDED "AS IS". JACKSON EXTENDS NO WARRANTIES OF ANY KIND, EITHER EXPRESS, IMPLIED, OR STATUTORY, WITH RESPECT TO MICE, PRODUCTS OR SERVICES, INCLUDING ANY IMPLIED WARRANTY OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE, OR ANY WARRANTY OF NON-INFRINGEMENT OF ANY PATENT, TRADEMARK, OR OTHER INTELLECTUAL PROPERTY RIGHTS.

Credit for PRODUCTS or SERVICES

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Animal Care and Use for SERVICES

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No Liability

In no event shall JACKSON, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, PRODUCTS, or SERVICES, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of JACKSON, its agents or employees. Unless prohibited by law, in purchasing or receiving MICE, PRODUCTS, or SERVICES from JACKSON, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges JACKSON from all such causes of action or damages, and further agrees to defend and indemnify JACKSON from any costs or damages arising out of any third party claims.

MICE, PRODUCTS or SERVICES are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to JACKSON’s MICE, PRODUCTS or SERVICES. In addition, special terms and conditions of sale of certain MICE, PRODUCTS, or SERVICES may be set forth separately in JACKSON web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, PRODUCTS and SERVICES by JACKSON, and by its licensees and distributors.

Acceptance of delivery of MICE, PRODUCTS or SERVICES shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on JACKSON, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, PRODUCTS or SERVICES by JACKSON.

Also Known As:nNOS KO

Donating Investigator

Genetic overview

Research Applications

Base Price

Important Note

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Nos1tm1Plh

Allele Symbol: Nos1tm1Plh

Disease Terms

Models with phenotypic similarity to human diseases where etiology is unknown or involving genes where ortholog is unknown.

No similarity to the expected human disease phenotype was found. One or more human genes are associated with this human disease. The mouse genotype may involve mutations to orthologs of one or more of these genes, but the phenotype did not resemble the disease.

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Genotype: Nos1tm1Plh related

Mammalian Phenotype Terms by Genotype

Genotype: Nos1tm1Plh/Nos1tm1Plhinvolves: 129S4/SvJae * C57BL/6

behavior/neurological phenotype

cardiovascular system phenotype

cellular phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

liver/biliary system phenotype

mammalian phenotype

mortality/aging

muscle phenotype

nervous system phenotype

renal/urinary system phenotype

reproductive system phenotype

respiratory system phenotype

Genotype: Nos1tm1Plh/Nos1tm1Plhinvolves: 129S4/SvJae

behavior/neurological phenotype

digestive/alimentary phenotype

cardiovascular system phenotype

growth/size/body region phenotype

hematopoietic system phenotype

homeostasis/metabolism phenotype

immune system phenotype

mammalian phenotype

mortality/aging

muscle phenotype

nervous system phenotype

cellular phenotype

Genotype: Nos1tm1Plh/Nos1tm1Plhinvolves: 129S4/SvJae * C57BL/6J

behavior/neurological phenotype

cardiovascular system phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

mammalian phenotype

muscle phenotype

renal/urinary system phenotype

Genotype: Nos1tm1Plh/Nos1tm1Plhinvolves: 129S4/SvJae * C57BL/10ScSn

mammalian phenotype

Genotype: Nos1tm1Plh/Nos1tm1PlhB6;129S4-Nos1/J

behavior/neurological phenotype

cellular phenotype

hematopoietic system phenotype

immune system phenotype

mammalian phenotype

nervous system phenotype

skeleton phenotype

Genotype: Nos1tm1Plh/Nos1tm1PlhB6.129S4-Nos1

behavior/neurological phenotype

cardiovascular system phenotype

cellular phenotype

homeostasis/metabolism phenotype

mammalian phenotype

nervous system phenotype

vision/eye phenotype

Genotype: Nos1tm1Plh/Nos1tm1PlhB6.129S4-Nos1/J

growth/size/body region phenotype

immune system phenotype

muscle phenotype

Nos1^tm1Plh

Allele Symbol: Nos1^tm1Plh

Genotype: Nos1^tm1Plh related

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae * C57BL/6

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae * C57BL/6J

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
involves: 129S4/SvJae * C57BL/10ScSn

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
B6;129S4-Nos1/J

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
B6.129S4-Nos1

Genotype: Nos1^tm1Plh/Nos1^tm1Plh
B6.129S4-Nos1/J

Genotype: Nos1^tm1Plh/Nos1⁺
B6.129S4-Nos1

Additional - Nos1^tm1Plh related