Overview

Also Known As: trk^TK

Mice homozygous for the Ntrk1^tm1 targeted mutation (commonly referred to as trkA) die by 2-3 weeks of age. Homozygous mutant mice show a complete lack of both nociceptive and superior cervical ganglion neurons.

Donating Investigator

Dr. Mariano Barbacid, Centro Nacional de Investigaciones Oncol

Genetic overview

Genetic Background	Generation

Ntrk1^tm1Bbd

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Ntrk1	neurotrophic tyrosine kinase, receptor, type 1

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Research Applications

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

Mice homozygous for the Ntrk1^tm1 targeted mutation (commonly referred to as trkA) die by 2-3 weeks of age. Homozygous mutant mice show a complete lack of both nociceptive and superior cervical ganglion neurons.

Development

Part of exons 6 and 7 of the Ntrk1 gene were replaced using a vector containing the neo resistance gene. The 129-derived D3 ES cell line was used. It has subsequently been bred to C57BL/6 mice.

Control Suggestions

Wild-type from the colony
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Smeyne RJ; Klein R; Schnapp A; Long LK; Bryant S; Lewin A; Lira SA; Barbacid M. 1994. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene [see comments] Nature 368(6468):246-9PubMed: 8145823 MGI: J:17194

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Genetics

Ntrk1^tm1Bbd

Allele Symbol: Ntrk1^tm1Bbd

Allele Name	targeted mutation 1, Mariano Barbacid
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	targeted mutation 1, Mariano Barbacid; Ntrk1^tm1Bbd
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
Strain of Origin	129S2/SvPas
Chromosome	3
Molecular Note	Sequences encoding 51 amino acids of the kinase catalytic domain were replaced with a neomycin cassette. RNase protection analysis on tissues isolated from homozygous mutant mice failed to identify any Ntrk1 transcripts.
Mutations Made By	Dr. Mariano Barbacid, Centro Nacional de Investigaciones Oncol

Disease/Phenotype

Disease Terms

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

hereditary sensory neuropathy

Research Areas By Genotype

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

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^tm1Bbd/Ntrk1^tm1Bbd
involves: 129S2/SvPas

behavior/neurological phenotype

abnormal vibrissae reflex
- at P10, homozygotes fail to orient in response to vibrissal stimulation

increased thermal nociceptive threshold
- at P10, homozygotes remain on a hot plate at 60 degrees Celsius for at least 10 sec, whereas wild-type and heterozygous mice jump off within 1-2 sec

unresponsive to tactile stimuli
- at p10, homozygotes fail to react to deep pinpricks in the their whisker pads and rear paws

mortality/aging

postnatal lethality, incomplete penetrance
- although normal at birth, about 50% of homozygotes die by P20

premature death
- no homozygotes survive beyond P55

nervous system phenotype

abnormal cholinergic neuron morphology
- adult homozygotes display a reduction in the cholinergic basal forebrain projections to the hippocampus and cerebral cortex

abnormal sympathetic ganglion morphology
- at P0, a number of sympathetic ganglia display neuronal loss

abnormal sympathetic nervous system physiology
- Normal - in contrast, the facial, acoustic and glossopharyngeal nerves function normally
- upon eye illumination, the iris constricts without efficient redilation, indicating that the parasympathetic component of the oculomotor nerve is intact but the sympathetic innervation from the superior cervical ganglion is defective

small dorsal root ganglion
- at P0, dorsal root ganglia show a 70-90% loss of neurons; small-sized neurons are preferentially lost

small superior cervical ganglion
- at P0, superior cervical ganglia (SCG) show neuronal loss as well as pyknotic nuclei, suggesting cellular degeneration
- by P10, the SGC is severely shrunken

small trigeminal ganglion
- at P0, trigeminal ganglia are significantly smaller and the number of trigeminal neurons is reduced by 70-90%
- Normal - other cranial ganglia appear normal

pigmentation phenotype

mottled coat
- at >3-4 weeks of age, homozygotes display a mottled fur

vision/eye phenotype

blepharoptosis
- by P20, surviving homozygotes exhibit slight ptosis

corneal opacity
- at >3-4 weeks, corneal opacities are observed

miotic pupils
- by P20, surviving homozygotes have myotic pupils

growth/size/body region phenotype

decreased body size
- at P10, homozygotes are noticeably smaller than wild-type mice

integument phenotype

increased thermal nociceptive threshold
- at P10, homozygotes remain on a hot plate at 60 degrees Celsius for at least 10 sec, whereas wild-type and heterozygous mice jump off within 1-2 sec

mottled coat
- at >3-4 weeks of age, homozygotes display a mottled fur

skin lesions
- at >3-4 weeks of age, homozygotes develop multiple scabs all over their body

unresponsive to tactile stimuli
- at p10, homozygotes fail to react to deep pinpricks in the their whisker pads and rear paws

limbs/digits/tail phenotype

abnormal digit morphology
- at >3-4 weeks, digits are missing, probably due to self-mutilation

ulcerated paws
- at >3-4 weeks, homozygotes display ulcerated paws

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

Genotype: Ntrk1^tm1Bbd/Ntrk1^tm1Bbd
involves: 129S2/SvPas * C57BL/6

mammalian phenotype

hearing/vestibular/ear phenotype
- Normal - at P1, newborn homozygotes exhibit normal neuron numbers in cochlear and vestibular ganglia as well as normal innervation patterns of cochlear and vestibular sensory epithelia relative to wild-type mice

References

Smeyne RJ; Klein R; Schnapp A; Long LK; Bryant S; Lewin A; Lira SA; Barbacid M. 1994. Severe sensory and sympathetic neuropathies in mice carrying a disrupted Trk/NGF receptor gene [see comments] Nature 368(6468):246-9PubMed: 8145823 MGI: J:17194

Additional References

Silos-Santiago I; Molliver DC; Ozaki S; Smeyne RJ; Fagan AM; Barbacid M; Snider WD. 1995. Non-TrkA-expressing small DRG neurons are lost in TrkA deficient mice. J Neurosci 15(9):5929-42PubMed: 7666178 MGI: J:28575
White FA; Silos-Santiago I; Molliver DC; Nishimura M; Phillips H; Barbacid M; Snider WD. 1996. Synchronous onset of NGF and TrkA survival dependence in developing dorsal root ganglia. J Neurosci 16(15):4662-72PubMed: 8764654 MGI: J:34321
Fagan AM; Zhang H; Landis S; Smeyne RJ; Silos-Santiago I; Barbacid M. 1996. TrkA, but not TrkC, receptors are essential for survival of sympathetic neurons in vivo. J Neurosci 16(19):6208-18PubMed: 8815902 MGI: J:35563

Additional - Ntrk1^tm1Bbd related

Technical Support

Contact Technical Support

Genotyping Protocols
- Separated PCR:Ntrk1^tm1Bbd
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, this mutant can be maintained by mating heterozygous siblings or by mating heterozygous mice with normal wildtype siblings. Homozygous mice die by 2-3 weeks of age.
- Additional Breeding and Husbandry Support
Citation
When using the trk^TK mouse strain in a publication, please cite the originating article(s) and include JAX stock #002480 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 or Wild-type for Ntrk1<tm1Bbd>

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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Licensing Information

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Also Known As: trkTK

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Additional Information

Selected References

Ntrk1tm1Bbd

Allele Symbol: Ntrk1tm1Bbd

Disease Terms

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

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Ntrk1tm1Bbd/Ntrk1tm1Bbdinvolves: 129S2/SvPas

behavior/neurological phenotype

mortality/aging

nervous system phenotype

pigmentation phenotype

vision/eye phenotype

growth/size/body region phenotype

integument phenotype

limbs/digits/tail phenotype

Genotype: Ntrk1tm1Bbd/Ntrk1tm1Bbdinvolves: 129S2/SvPas * C57BL/6

mammalian phenotype

References

Additional References

Additional - Ntrk1tm1Bbd 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

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

Also Known As: trk^TK

Ntrk1^tm1Bbd

Allele Symbol: Ntrk1^tm1Bbd

Genotype: Ntrk1^tm1Bbd/Ntrk1^tm1Bbd
involves: 129S2/SvPas

Genotype: Ntrk1^tm1Bbd/Ntrk1^tm1Bbd
involves: 129S2/SvPas * C57BL/6

Additional - Ntrk1^tm1Bbd related