Overview

This targeted mutation of the neurturin (Nrtn) gene displays reductions in neuron fiber density and neuronal size in the enteric nervous system, reduced gut motility, reduced parasympathetic and sensory innervation and may be useful in studies of the enteric, parasympathetic and sensory nervous systems

Donating Investigator

Jeffrey Milbrandt, Washington University School of Medicine, St. Louis

Genetic overview

Genetic Background	Generation

Nrtn^tm1Jmi

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Nrtn	neurturin

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Research Applications

Sensorineural Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice that are homozygous for the targeted mutation are viable, fertile and normal in size. Homozygotes exhibit a decrease in small fiber density in the small intestine, colon and duodenum, reduced myenteric ganglion cell size, and reduced gut motility. By two months of age, mice can be identified by eyelid droopiness, crusting around the eye, eyelid thickening and reduced tear production most likely the result of reduced parasympathetic innervation of the lacrimal gland. Parasympathetic neurons in the submandibular salivary gland and the ciliary ganglion are reduced in number, despite apparently normal function. Otic ganglion cells are reduced in size, but not in number. This mutant mouse strain may be useful in studies of the enteric, parasympathetic and sensory nervous systems.

Development

A targeting vector containing the neomycin resistance gene was used to disrupt a 1.5 kb region including entire coding region of the protein and extending into the 3' untranslated region. The construct was electroporated into 129X1/SvJ-derived RW4 embryonic stem (ES) cells. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric animals were crossed to C57BL/6J and maintained by intercross. Upon arrival, mice were bred to C57BL/6 for at least 1 generation to establish the colony.

Control Suggestions

None Available

Additional Information

Considerations for Choosing Controls

Selected References

Heuckeroth RO; Enomoto H; Grider JR; Golden JP; Hanke JA; Jackman A; Molliver DC; Bardgett ME; Snider WD; Johnson EM Jr; Milbrandt J. 1999. Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons [see comments] Neuron 22(2):253-63PubMed: 10069332 MGI: J:53261

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Genetics

Nrtn^tm1Jmi

Allele Symbol: Nrtn^tm1Jmi

Allele Name	targeted mutation 1, Jeffrey Milbrandt
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Nrtn^tm1Jmi; targeted mutation 1, Jeffrey Milbrandt
Gene Symbol and Name	Nrtn, neurturin
Gene Synonym(s)	NTN
Strain of Origin	129X1/SvJ
Chromosome	17
Molecular Note	The gene was disrupted by replacement of the entire coding region with a neomycin resistance cassette via homologous recombination. Absence of gene expression in homozygous mutant animals was confirmed by RT-PCR analysis of heart mRNA.
Mutations Made By	Jeffrey Milbrandt, Washington University School of Medicine, St. Louis

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Sensorineural Research
Neurobiology Research

Mammalian Phenotype Terms by Genotype

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

Genotype: Nrtn^tm1Jmi/Nrtn^tm1Jmi
involves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

abnormal blinking
- reduced blink reflex due to abnormal corneal sensation

nervous system phenotype

abnormal ciliary ganglion morphology
- reduced number of ciliary ganglion neurons but pupil function is normal

abnormal enteric neuron morphology
- 35% fewer small bowel submucosal neurons, however the number of colonic submucosal neurons and colon and small bowel myenteric neurons is normal
- decreased small fiber density in the small intestine and colon (by 40% in duodenum)
- density of acetylcholinesterase-stained neuronal fibers in the myenteric plexus is reduced by 32% in the small bowel and 22% in the colon
- myenteric neuron size is reduced by 29% in the small bowel and 33% in the colon, however submucosal neuron size is normal

abnormal lacrimal gland innervation pattern
- nerve fibers are almost completely absent in the lacrimal gland of adult mice, indicating reduced parasympathetic innervation to the lacrimal gland

abnormal neurotransmitter secretion
- 70-95% reduction in substance P and 35-70% reduction in VIP release

abnormal otic ganglion morphology
- otic ganglion cell size reduced but numbers of cells is normal

abnormal parasympathetic neuron morphology

abnormal parasympathetic postganglionic fiber morphology
- parasympathetic innervation of glandular tissue in reproductive organs lost
- severe reduction or lack of innervation to the lacrimal gland
- submandibular gland neurons smaller and fibers thinner

digestive/alimentary phenotype

intestinal hypoperistalsis
- decrease in both longitudinal and circular muscle contraction of the intestine in response to electric field stimulation

reproductive system phenotype

abnormal prostate gland epithelium morphology
- decreased mucosal thickening and folding in the secretory epithelium of the ventral prostate

vision/eye phenotype

abnormal conjunctiva goblet cell morphology
- significantly reduced number of globlet cells in the bulbar and tarsal conjunctiva

abnormal corneal epithelium morphology
- leukocytes found in epithelium

abnormal eye morphology

abnormal eye physiology
- permeability of corneal epithelium increased

abnormal lacrimal gland physiology
- crusting drainage

blepharoptosis
- drooping, thickened eyelids by 2 months of age

decreased tear production
- reduced aqueous tear production becoming significant at 8 weeks
- significantly delayed tear fluorescein clearance at >8 weeks

dry eyes

enophthalmos
- eyes set more deeply in sockets

increased corneal epithelium thickness
- thickened at 10 weeks from 5 layers to 8 with a basal cell phenotype

increased incidence of corneal inflammation
- Il-1beta levels significantly increased by 4 months of age

keratoconjunctivitis sicca
- mice display phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca

thick eyelids
- eyelid thickening in most mice by 2 months of age

endocrine/exocrine gland phenotype

abnormal lacrimal gland physiology
- crusting drainage

abnormal prostate gland epithelium morphology
- decreased mucosal thickening and folding in the secretory epithelium of the ventral prostate

immune system phenotype

increased incidence of corneal inflammation
- Il-1beta levels significantly increased by 4 months of age

keratoconjunctivitis sicca
- mice display phenotypic changes and ocular surface inflammation that mimic human keratoconjunctivitis sicca

muscle phenotype

impaired smooth muscle contractility
- contractile strength of stimulated gut muscles considerably reduced
- muscle strips from the gut with reduced spontaneous contractile activity

intestinal hypoperistalsis
- decrease in both longitudinal and circular muscle contraction of the intestine in response to electric field stimulation

References

Heuckeroth RO; Enomoto H; Grider JR; Golden JP; Hanke JA; Jackman A; Molliver DC; Bardgett ME; Snider WD; Johnson EM Jr; Milbrandt J. 1999. Gene targeting reveals a critical role for neurturin in the development and maintenance of enteric, sensory, and parasympathetic neurons [see comments] Neuron 22(2):253-63PubMed: 10069332 MGI: J:53261

Additional - Nrtn^tm1Jmi related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR: Nrtn^tm1Jmi
- Genotyping resources and troubleshooting
Breeding Considerations

While maintaining a live colony, these mice are bred as homozygotes.
- Additional Breeding and Husbandry Support
Citation
When using the B6;129X1-Nrtn^tm1Jmi/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #012238 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

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

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Heterozygous for Nrtn<tm1Jmi>

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.

Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.

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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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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Nrtntm1Jmi

Allele Symbol: Nrtntm1Jmi

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Nrtntm1Jmi/Nrtntm1Jmiinvolves: 129X1/SvJ * C57BL/6

behavior/neurological phenotype

nervous system phenotype

digestive/alimentary phenotype

reproductive system phenotype

vision/eye phenotype

endocrine/exocrine gland phenotype

immune system phenotype

muscle phenotype

References

Additional - Nrtntm1Jmi related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

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

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Nrtn^tm1Jmi

Allele Symbol: Nrtn^tm1Jmi

Genotype: Nrtn^tm1Jmi/Nrtn^tm1Jmi
involves: 129X1/SvJ * C57BL/6

Additional - Nrtn^tm1Jmi related