Overview

These mice carry a hypomorphic floxed F592A mutation in mouse Ntrk1 (neurotrophic tyrosine kinase, receptor, type 1; also called TrkA). Signaling is effectively blocked by application of 1NMPP1. This strain is useful in studies of nerve growth and survival.

Donating Investigator

David D. Ginty, Harvard Medical School

Genetic overview

Genetic Background	Generation

Ntrk1^tm1Ddg

Allele Type	Gene Symbol	Gene Name
Targeted (Not Specified)	Ntrk1	neurotrophic tyrosine kinase, receptor, type 1

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Research Applications

Neurobiology Research
Research Tools
Cell Biology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Ntrk1 (neurotrophic tyrosine kinase, receptor, type 1; also called TrkA) is a receptor for nerve growth factor (Ngf), a neurotrophin which controls aspects of mammalian nervous system development. NGF-NTRK1 (NGF-TrkA) signaling is crucial for the survival and growth of sympathetic neurons as well as small-diameter nociceptive sensory neurons.

These mice carry a floxed F592A mutation in exon 12 of the mouse Ntrk1 gene. The allele is sensitive to a family of small-molecule inhibitors including 1NaPP1 and 1NMPP1 which act selectively, rapidly and reversibly. Without 1NaPP1 or 1NMPP1 application, homozygous mutant mice are hypomorphic, with an approximate 50% reduction of both the number of calcitonin gene-related peptide (CGRP) and Ret-positive neurons in dorsal root ganglion and a reduction of peripheral innervation of both sensory and sympathetic fibers. Although hypomorphic, the mutants are viable and fertile, and signaling is effectively blocked by application of 1NMPP1. In sympathetic neurons cultured from mutant mice, NGF-dependent survival is robustly and specifically blocked by nanomolar concentrations of 1NMPP1 or 1NaPP1. 1NMPP1 application during pregnancy leads loss of superior cervical ganglion neurons. 1NMPP1 treatment during adulthood leads to axon terminal degeneration of a selective group of small-diameter peptidergic sensory neurons.

Development

An F592A (phenylalanine to alanine) mutation was generated in exon 12 to disrupt an ATP binding pocket, and an FRT-flanked neomycin cassette was placed in intron 12. A segment including exons 7-12 and the neomycin cassette was flanked by loxP sites. The mutation was made in 129P2/OlaHsd-derived GK129 embryonic stem (ES) cells. Heterozygotes were bred with C57BL/6-backcrossed mice bearing Tg(ACTFLPe)9205Dym to excise the FRT-flanked neomycin cassette. This strain was backcrossed to C57BL/6 for approximately 6 generations by the donating lab.

Control Suggestions

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Liuzzi JP; Lichten LA; Rivera S; Blanchard RK; Aydemir TB; Knutson MD; Ganz T; Cousins RJ. 2005. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A 102(19):6843-8PubMed: 15863613 MGI: J:99063

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Genetics

Ntrk1^tm1Ddg

Allele Symbol: Ntrk1^tm1Ddg

Allele Name	targeted mutation 1, David D Ginty
Allele Type	Targeted (Not Specified)
Allele Synonym(s)	Ntrk1^tm1Ddg; targeted mutation 1, David D Ginty
Gene Symbol and Name	Ntrk1, neurotrophic tyrosine kinase, receptor, type 1
Gene Synonym(s)	MTC; TRK; Trk-A; TRK1; TRKA; Tkr; p140-TrkA; Tkr; C80751; tyrosine kinase receptor proto-oncogene; expressed sequence C80751; Trk; TrkA
Promoter	Ntrk1, neurotrophic tyrosine kinase, receptor, type 1, mouse, laboratory
Strain of Origin	129P2/OlaHsd
Chromosome	3
Molecular Note	A phenylalanine to alanine substitution mutation at residue 592 (F592A) was introduced via homologous recombination using a mutagenized construct with an FRT flanked neomycin resistance tag. Heterozygotes were bred with mice bearing Tg(ACTFLPe)9205Dym which expressed FLP1 recombinase. The resulting allele has the F592A mutation but the neomycin resistance cassete has been excised.
Mutations Made By	David Ginty, Harvard Medical School

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Neurodevelopmental Defects
- Cre-lox System
  - loxP-flanked Sequences
Research Tools
- Cre-lox System
  - loxP-flanked Sequences
Cell Biology Research
- Signal Transduction

Mammalian Phenotype Terms by Genotype

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

Genotype: Ntrk1^tm1Ddg/Ntrk1^tm1Ddg
involves: 129P2/OlaHsd * C57BL/6

normal phenotype

no abnormal phenotype detected
- Normal - viable and fertile, with no obvious behavioral abnormalities, however NMPP1, a derivative of the general kinase inhibitor PP1, inhibits neurotrophin signaling in neurons unlike in wild-type

References

Liuzzi JP; Lichten LA; Rivera S; Blanchard RK; Aydemir TB; Knutson MD; Ganz T; Cousins RJ. 2005. Interleukin-6 regulates the zinc transporter Zip14 in liver and contributes to the hypozincemia of the acute-phase response. Proc Natl Acad Sci U S A 102(19):6843-8PubMed: 15863613 MGI: J:99063

Additional - Ntrk1^tm1Ddg related

Technical Support

Contact Technical Support

Genotyping Protocols
- Standard PCR:Ntrk1^tm1Ddg
- Genotyping resources and troubleshooting
Breeding Considerations

Homozygotes and heterozygotes are viable and fertile.
- Additional Breeding and Husbandry Support
Citation
When using the B6.129P2(SJL)-Ntrk1^tm1Ddg/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #022362 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 Ntrk1<tm1Ddg>

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.

Related Products and Services

Frozen Mouse Embryo	B6.129P2(SJL)-Ntrk1<tm1Ddg>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2(SJL)-Ntrk1<tm1Ddg>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	B6.129P2(SJL)-Ntrk1<tm1Ddg>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	B6.129P2(SJL)-Ntrk1<tm1Ddg>/J Frozen Embryo	$3373.50

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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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Licensing Information

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ntrk1tm1Ddg

Allele Symbol: Ntrk1tm1Ddg

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ntrk1tm1Ddg/Ntrk1tm1Ddginvolves: 129P2/OlaHsd * C57BL/6

normal phenotype

References

Additional - Ntrk1tm1Ddg 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

Ntrk1^tm1Ddg

Allele Symbol: Ntrk1^tm1Ddg

Genotype: Ntrk1^tm1Ddg/Ntrk1^tm1Ddg
involves: 129P2/OlaHsd * C57BL/6

Additional - Ntrk1^tm1Ddg related