Overview

Head tilt (Nox3^het) is an autosomal recessive mutation that can cause abnormal circling behavior and hyperactivity in affected mice. Homozygotes also exhibit a subtle head tilt. Together, the abnormal behavioral phenotype is consistent with that of a vestibular disorder. Evoked auditory brainstem response profiles are normal indicating that the mutants are not deaf. Nox3^het/Nox3^het mutants are unable to sense orientation under water and therefore, cannot swim properly. If held by the tail, Nox3^het/Nox3^het mice retract, rather than extend, their limbs; they also flex ventrally, instead of dorsally as wild type mice do. When lowered quickly by the tail, Nox3^het/Nox3^het mice fail to extend their forelimbs in a normal manner and have difficulty righting themselves if dropped vertically from a short distance. Morphological assessment of the inner ear of homozygotes r...

Genetic overview

Genetic Background	Generation

Nox3^het

Allele Type	Gene Symbol	Gene Name
Spontaneous	Nox3	NADPH oxidase 3

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Research Applications

Sensorineural Research
Neurobiology Research
Internal/Organ Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Head tilt (Nox3^het) is an autosomal recessive mutation that can cause abnormal circling behavior and hyperactivity in affected mice. Homozygotes also exhibit a subtle head tilt. Together, the abnormal behavioral phenotype is consistent with that of a vestibular disorder. Evoked auditory brainstem response profiles are normal indicating that the mutants are not deaf. Nox3^het/Nox3^het mutants are unable to sense orientation under water and therefore, cannot swim properly. If held by the tail, Nox3^het/Nox3^het mice retract, rather than extend, their limbs; they also flex ventrally, instead of dorsally as wild type mice do. When lowered quickly by the tail, Nox3^het/Nox3^het mice fail to extend their forelimbs in a normal manner and have difficulty righting themselves if dropped vertically from a short distance. Morphological assessment of the inner ear of homozygotes reveals an abnormal appearance of the saccule and utricle owing to a complete absence of otoliths. Otoliths are tiny calciferous granules within the statoconic membrane that covers the sensory epithelia of the acoustic maculae. These ear crystals function as mass particles that stimulate gravity receptors in the maculae of the utricle and saccule in response to head tilting and gravitational forces. Electrophysiological assessment of the vestibular neurons in Nox3^het mutants demonstrates these cells totally lack vestibular evoked potentials in response to pulsed linear acceleration. Thus, the mutants are unable to process ostolite-mediated sensory stimuli throughout their entire lifespan. The Nox3^het gene product is likely involved in the formation of the otolithic ear crystals (prior to embryonic day 14), perhaps through the regulation of calcium secretion by neuroepithelial cells. Structures of the cochlea and middle ear appear normal and melanocyte function is not compromised.(Sweet, 1980; Bergstrom et al., 1998; Jones et al., 1999)

Development

The Nox3^het mutation arose spontaneously at the Jackson Laboratory in 1975 in the GL/Le inbred strain (Stock No. 000255) which was then at F25. In 1976, a male Nox3^het/Nox3^het (F27) was outcrossed once to the F1 hybrid C3B6A/A^w-J to separate Nox3^het from downless Jackson (Edar^dl-J) and grey lethal (gl). The strain was maintained by sibling mating thereafter. In 1983, embryos derived from homozygous F30 C3B6A/A^w-J-Nox3^het males crossed to C57BL/6J dams were cryopreserved. gl and Edar^dl-J have not been detected in the stock since F2.

Genetics

Nox3^het

Allele Symbol: Nox3^het

Allele Name	head-tilt
Allele Type	Spontaneous
Allele Synonym(s)	Nox3^het; head-tilt
Gene Symbol and Name	Nox3, NADPH oxidase 3
Gene Synonym(s)	het; nmf250; nmf250; het; MOX-2; head-tilt; neuroscience mutagenesis facility, 250; GP91-3
Strain of Origin	GL/Le
Chromosome	17
Molecular Note	The mutation in the het mouse was identified as retroviral insertion into intron 12, resulting in aberrant splicing.

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Genotype: Nox3^het related

Sensorineural Research
- Vestibular Defects
Neurobiology Research
- Circadian Rhythms
Internal/Organ Research
- Adipose 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: Nox3^het/Nox3^het
involves: GL/Le

behavior/neurological phenotype

circling

head tilt

hyperactivity

impaired swimming

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - mutants are not deaf

Genotype: Nox3^het/Nox3^het
B6Ei.GL-Nox3/J

adipose tissue phenotype

decreased total body fat amount
- percent body fat did not differ significantly between 1G and 2G mutants
- percent body fat was significantly lower in mutants
- percent lean mass did not differ significantly between 1G and 2G mutants
- percent lean mass was significantly higher in mutants

growth/size/body region phenotype

decreased body weight
- the body mass of mutants is slightly less than that of wild-types
- the drop in body mass following onset of 2 gravities (2G) is significantly less for mutants than wild-types
- the drop in body mass for mutants following onset of 2G is transient and not significantly different from 1G controls while the drop in body mass for wild-types is sustained and significantly different from 1G controls

hearing/vestibular/ear phenotype

absent linear vestibular evoked potential
- mutants have no measurable vestibular evoked potential in response to linear acceleration

absent otoliths
- mutants displayed normal response to auditory stimuli
- no other inner ear abnormalities were found
- the otoliths are bilaterally absent

absent vestibuloocular reflex
- in both cases the response of these mutants is less at lower rotational frequencies
- the mutants exhibit almost no or highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate both the otoliths and semicircular canals (vestibulo ocular reflex)
- the mutants exhibit highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate only the only semicircular canals
- these results suggest these mutants lack canal mediated vestibulo ocular reflex and have deficient semicircular canal mediated vestibulo ocular reflex

homeostasis/metabolism phenotype

abnormal circadian temperature homeostasis
- at the onset of 2G mutants do not have a large drop in body temperature unlike wild-types
- the amplitude of body temperature circadian rhythm was significantly larger in mutants
- this is largely attributable to lower mean resting body temperature in mutants

behavior/neurological phenotype

abnormal circadian behavior
- the amplitude of activity circadian rhythm was significantly larger in mutants

abnormal food intake
- the decrease in food intake following onset of 2G is smaller and delayed in mutants than in wildtypes
- under normal (1G) conditions food intake does not differ between mutants and wild-types

absent vestibuloocular reflex
- in both cases the response of these mutants is less at lower rotational frequencies
- the mutants exhibit almost no or highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate both the otoliths and semicircular canals (vestibulo ocular reflex)
- the mutants exhibit highly attenuated compensatory eye movements with significant phase errors in response to motions designed to stimulate only the only semicircular canals
- these results suggest these mutants lack canal mediated vestibulo ocular reflex and have deficient semicircular canal mediated vestibulo ocular reflex

altered righting response
- young mutant pups (1 - 3 weeks old) had difficulty rolling over and righting when disturbed

circling
- increased rarity of circling behaviour in mutants from The Jackson Laboratory compared to those from Harwell possibly as a result of differences in background

head tilt

impaired swimming
- mutants are unable to swim or float

References

Additional References

Bergstrom RA; You Y; Erway LC; Lyon MF; Schimenti JC. 1998. Deletion mapping of the head tilt (het) gene in mice: a vestibular mutation causing specific absence of otoliths. Genetics 150(2):815-22PubMed: 9755211 MGI: J:50247
Jones SM; Erway LC; Bergstrom RA; Schimenti JC; Jones TA. 1999. Vestibular responses to linear acceleration are absent in otoconia-deficient C57BL/6JEi-het mice. Hear Res 135(1-2):56-60PubMed: 10491954 MGI: J:59485

Additional - Nox3^het related

Technical Support

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Genotyping Protocols
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Appearance
- agouti, unaffected
  Related Genotype: A/A Nox3^het/+ or A/A +/+
  
  white-bellied agouti, unaffected
  Related Genotype: A/A^w-J Nox3^het/+ or A/A^w-J + + or A^w-J/A^w-J Nox3^het/+ or A^w-J/A^w-J +/+
  
  agouti, circling
  Related Genotype: A/A Nox3^het/Nox3^het
  
  white-bellied agouti, circling
  Related Genotype: A/A^w-J Nox3^het/Nox3^het or A^w-J/A^w-J het/Nox3^het
Citation
When using the B6 x STOCK Nox3^het/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #000061 in your Materials and Methods section.

Animal Health Reports

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Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

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We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

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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.

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Genetic overview

Research Applications

Base Price

Detailed Description

Development

Nox3het

Allele Symbol: Nox3het

Disease Terms

Research Areas By Genotype

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

Genotype: Nox3het related

Mammalian Phenotype Terms by Genotype

Genotype: Nox3het/Nox3hetinvolves: GL/Le

behavior/neurological phenotype

mammalian phenotype

Genotype: Nox3het/Nox3hetB6Ei.GL-Nox3/J

adipose tissue phenotype

growth/size/body region phenotype

hearing/vestibular/ear phenotype

homeostasis/metabolism phenotype

behavior/neurological phenotype

References

Additional References

Additional - Nox3het related

Genotyping Protocols

Appearance

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Nox3^het

Allele Symbol: Nox3^het

Genotype: Nox3^het related

Genotype: Nox3^het/Nox3^het
involves: GL/Le

Genotype: Nox3^het/Nox3^het
B6Ei.GL-Nox3/J

Additional - Nox3^het related