Strain Name:

B6;129S2-Ntrk3tm1Bbd/J

Stock Number:

002481

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Availability:

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Description

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Strain Information

Former Names TRKC    (Changed: 15-DEC-04 )
Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
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Specieslaboratory mouse
 
Donating InvestigatorDr. Mariano Barbacid,   Centro Nacional de Investigaciones Oncol

Description
Mice homozygous for this Ntrk3tm1 targeted mutation (commonly referred to as trkC) die by 2-3 weeks of age. Homozygous mutant mice lack proprioceptive and cochlear neurons and have a reduction in vestibular neurons.

Development
Part of exon K2 of the Ntrk3 gene was replaced using a vector containing the neo resistance gene. This strain was generated on a 129 genetic background. It has subsequently been bred to C57BL/6 mice.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls

Related Strains

Strains carrying other alleles of Ntrk3
022364   B6.129P2(SJL)-Ntrk3tm1Ddg/J
View Strains carrying other alleles of Ntrk3     (1 strain)

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Ntrk3tm1Bbd/Ntrk3tm1Bbd

        involves: 129S2/SvPas * C57BL/6
  • mortality/aging
  • postnatal lethality
    • most homozygotes die by P21   (MGI Ref ID J:17195)
  • premature death
    • a few homozygotes live up to 4 months or longer   (MGI Ref ID J:17195)
  • behavior/neurological phenotype
  • *normal* behavior/neurological phenotype
    • homozygotes respond normally to painful stimuli in their whisker pads as well as to pinching of their tail and foot   (MGI Ref ID J:17195)
    • athetotic walking movements
      • by P10, homozygotes display athetotic walking movements   (MGI Ref ID J:17195)
    • impaired coordination
      • on a rotating dowel, homozygotes fail to maintain an upright posture and tumble off   (MGI Ref ID J:17195)
    • impaired limb coordination
      • even at rest, the limbs are held in abnormal positions in relation to the trunk   (MGI Ref ID J:17195)
    • limb grasping
      • when hung by the tail, homozygotes draw their limbs in towards their bodies   (MGI Ref ID J:17195)
  • nervous system phenotype
  • abnormal sensory neuron innervation pattern
    • homozygotes lack Ia muscle afferent projections to spinal motor neurons and have fewer large myelinated axons in the dorsal root and posterior columns of the spinal cord   (MGI Ref ID J:17195)
    • abnormal cochlear IHC afferent innervation pattern
      • at P1, IHCs are devoid of innervation   (MGI Ref ID J:29245)
      • developmental analysis indicates that, at E16.5, some cochlear nerve fibers initially reach their peripheral targets but subsequently fail to maintain innervation and degenerate   (MGI Ref ID J:29245)
      • in contrast, the innervation pattern of OHCs appears normal   (MGI Ref ID J:29245)
  • small cochlear ganglion
    • at P1, a 51% reduction in cochlear ganglion neuron number is observed   (MGI Ref ID J:29245)
    • large-sized type I neurons (innervating IHCs) are preferentially lost (62% reduction), whereas small-sized type II neurons (innervating OHCs) remain unaffected   (MGI Ref ID J:29245)
  • small dorsal root ganglion
    • newborn homozygotes show a 19% neuron loss in the lumbar dorsal root ganglia   (MGI Ref ID J:17195)
  • small vestibular ganglion
    • by P1, a 16% reduction in vestibular ganglion neuron number is observed   (MGI Ref ID J:29245)
    • however, both vestibular ganglia and vestibular sensory epithelia are histologically normal and their innervation patterns appear unaffected   (MGI Ref ID J:29245)
  • hearing/vestibular/ear phenotype
  • abnormal cochlear sensory epithelium morphology
    • at P1, the cochlear sensory epithelium appears thinner and less stratified than normal   (MGI Ref ID J:29245)
    • abnormal cochlear IHC afferent innervation pattern
      • at P1, IHCs are devoid of innervation   (MGI Ref ID J:29245)
      • developmental analysis indicates that, at E16.5, some cochlear nerve fibers initially reach their peripheral targets but subsequently fail to maintain innervation and degenerate   (MGI Ref ID J:29245)
      • in contrast, the innervation pattern of OHCs appears normal   (MGI Ref ID J:29245)
  • growth/size/body phenotype
  • decreased body size
    • although normal at birth, homozygotes exhibit reduced body size at P4   (MGI Ref ID J:17195)
View Research Applications

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

Ntrk3tm1Bbd related

Cancer Research
Growth Factors/Receptors/Cytokines

Immunology, Inflammation and Autoimmunity Research
Growth Factors/Receptors/Cytokines

Neurobiology Research
Hearing Defects
Neurotrophic Factor Defects
Receptor Defects

Sensorineural Research
Hearing Defects

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Ntrk3tm1Bbd
Allele Name targeted mutation 1, Mariano Barbacid
Allele Type Targeted (Null/Knockout)
Common Name(s) trkC-; trkCTK; trkCK-;
Mutation Made ByDr. Mariano Barbacid,   Centro Nacional de Investigaciones Oncol
Strain of Origin129S2/SvPas
ES Cell Line NameD3
ES Cell Line Strain129S2/SvPas
Gene Symbol and Name Ntrk3, neurotrophic tyrosine kinase, receptor, type 3
Chromosome 7
Gene Common Name(s) AW125844; TRKC; expressed sequence AW125844; gp145(trkC);
Molecular Note Insertion of a neomycin cassette into exon K2, which encodes part of the kinase domain of the protein. An alternatively spliced mRNA was detectable in an RNase protection analysis on tissues derived from homozygous mutant mice; these transcripts splicedfrom exon K1 to K3. A partial protein product is predicted to be expressed from this allele. [MGI Ref ID J:17195]

Genotyping

Genotyping Information

Genotyping Protocols

Ntrk3tm1Bbd, Standard PCR
NEOTD (Generic Neo), Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Klein R; Silos-Santiago I; Smeyne RJ; Lira SA; Brambilla R; Bryant S; Zhang L; Snider WD; Barbacid M. 1994. Disruption of the neurotrophin-3 receptor gene trkC eliminates la muscle afferents and results in abnormal movements [see comments] Nature 368(6468):249-51. [PubMed: 8145824]  [MGI Ref ID J:17195]

Additional References

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):6208-18. [PubMed: 8815902]  [MGI Ref ID J:35563]

Minichiello L; Piehl F; Vazquez E; Schimmang T; Hokfelt T; Represa J; Klein R. 1995. Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons. Development 121(12):4067-75. [PubMed: 8575307]  [MGI Ref ID J:30344]

Schimmang T; Minichiello L; Vazquez E; San Jose I; Giraldez F; Klein R; Represa J. 1995. Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targets. Development 121(10):3381-91. [PubMed: 7588071]  [MGI Ref ID J:29245]

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):4662-72. [PubMed: 8764654]  [MGI Ref ID J:34321]

Ntrk3tm1Bbd related

Botchkareva NV; Botchkarev VA; Metz M; Silos-Santiago I; Paus R. 1999. Retardation of hair follicle development by the deletion of TrkC, high-affinity neurotrophin-3 receptor. J Invest Dermatol 113(3):425-7. [PubMed: 10469347]  [MGI Ref ID J:118909]

Calella AM; Nerlov C; Lopez RG; Sciarretta C; von Bohlen und Halbach O; Bereshchenko O; Minichiello L. 2007. Neurotrophin/Trk receptor signaling mediates C/EBPalpha, -beta and NeuroD recruitment to immediate-early gene promoters in neuronal cells and requires C/EBPs to induce immediate-early gene transcription. Neural Dev 2:4. [PubMed: 17254333]  [MGI Ref ID J:160655]

Cronk KM; Wilkinson GA; Grimes R; Wheeler EF; Jhaveri S; Fundin BT; Silos-Santiago I; Tessarollo L; Reichardt LF; Rice FL. 2002. Diverse dependencies of developing Merkel innervation on the trkA and both full-length and truncated isoforms of trkC. Development 129(15):3739-50. [PubMed: 12117822]  [MGI Ref ID J:77445]

Eng S; Gratwick K; Rhee J; Fedtsova N; Gan L; Turner E. 2001. Defects in sensory axon growth precede neuronal death in Brn3a-deficient mice. J Neurosci 21(2):541-9. [PubMed: 11160433]  [MGI Ref ID J:67059]

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):6208-18. [PubMed: 8815902]  [MGI Ref ID J:35563]

Fritzsch B; Barbacid M; Silos-Santiago I. 1998. The combined effects of trkB and trkC mutations on the innervation of the inner ear. Int J Dev Neurosci 16(6):493-505. [PubMed: 9881298]  [MGI Ref ID J:52165]

Fukuhara K; Imai F; Ladle DR; Katayama K; Leslie JR; Arber S; Jessell TM; Yoshida Y. 2013. Specificity of monosynaptic sensory-motor connections imposed by repellent Sema3E-PlexinD1 signaling. Cell Rep 5(3):748-58. [PubMed: 24210822]  [MGI Ref ID J:205528]

Fundin BT; Silos-Santiago I; Ernfors P; Fagan AM; Aldskogius H ; DeChiara TM ; Phillips HS ; Barbacid M ; Yancopoulos GD ; Rice FL. 1997. Differential dependency of cutaneous mechanoreceptors on neurotrophins, trk receptors, and P75 LNGFR. Dev Biol 190(1):94-116. [PubMed: 9331334]  [MGI Ref ID J:43425]

Furlan A; Lubke M; Adameyko I; Lallemend F; Ernfors P. 2013. The transcription factor Hmx1 and growth factor receptor activities control sympathetic neurons diversification. EMBO J 32(11):1613-25. [PubMed: 23591430]  [MGI Ref ID J:198834]

Holm PC; Rodriguez FJ; Kresse A; Canals JM; Silos-Santiago I; Arenas E. 2003. Crucial role of TrkB ligands in the survival and phenotypic differentiation of developing locus coeruleus noradrenergic neurons. Development 130(15):3535-45. [PubMed: 12810600]  [MGI Ref ID J:83661]

Ichikawa H; Matsuo S; Silos-Santiago I; Jacquin MF; Sugimoto T. 2001. Developmental dependency of Merkel endings on trks in the palate. Brain Res Mol Brain Res 88(1-2):171-5. [PubMed: 11295244]  [MGI Ref ID J:109307]

Ichikawa H; Matsuo S; Silos-Santiago I; Jacquin MF; Sugimoto T. 2004. The development of myelinated nociceptors is dependent upon trks in the trigeminal ganglion. Acta Histochem 106(5):337-43. [PubMed: 15530548]  [MGI Ref ID J:101950]

Ichikawa H; Matsuo S; Silos-Santiago I; Sugimoto T. 2000. Developmental dependency of Meissner corpuscles on trkB but not trkA or trkC Neuroreport 11(2):259-62. [PubMed: 10674466]  [MGI Ref ID J:60480]

Kim JY; Nelson AL; Algon SA; Graves O; Sturla LM; Goumnerova LC; Rowitch DH; Segal RA; Pomeroy SL. 2003. Medulloblastoma tumorigenesis diverges from cerebellar granule cell differentiation in patched heterozygous mice. Dev Biol 263(1):50-66. [PubMed: 14568546]  [MGI Ref ID J:86153]

Kucera J; Fan G; Walro J; Copray S; Tessarollo L; Jaenisch R. 1998. Neurotrophin-3 and trkC in muscle are non-essential for the development of mouse muscle spindles. Neuroreport 9(5):905-9. [PubMed: 9579688]  [MGI Ref ID J:47110]

Lee J; Friese A; Mielich M; Sigrist M; Arber S. 2012. Scaling proprioceptor gene transcription by retrograde NT3 signaling. PLoS One 7(9):e45551. [PubMed: 23029089]  [MGI Ref ID J:191993]

Martinez A; Alcantara S; Borrell V; Del Rio JA; Blasi J; Otal R; Campos N; Boronat A; Barbacid M; Silos-Santiago I; Soriano E. 1998. TrkB and TrkC signaling are required for maturation and synaptogenesis of hippocampal connections. J Neurosci 18(18):7336-50. [PubMed: 9736654]  [MGI Ref ID J:49747]

Matsuo S; Ichikawa H; Silos-Santiago I; Arends JJ; Henderson TA; Kiyomiya K; Kurebe M; Jacquin MF. 2000. Proprioceptive afferents survive in the masseter muscle of trkC knockout mice. Neuroscience 95(1):209-16. [PubMed: 10619477]  [MGI Ref ID J:60077]

Metz M; Botchkarev VA; Botchkareva NV; Welker P; Tobin DJ; Knop J; Maurer M; Paus R. 2004. Neurotrophin-3 regulates mast cell functions in neonatal mouse skin. Exp Dermatol 13(5):273-81. [PubMed: 15140017]  [MGI Ref ID J:137412]

Minichiello L; Klein R. 1996. TrkB and TrkC neurotrophin receptors cooperate in promoting survival of hippocampal and cerebellar granule neurons. Genes Dev 10(22):2849-58. [PubMed: 8918886]  [MGI Ref ID J:36756]

Minichiello L; Piehl F; Vazquez E; Schimmang T; Hokfelt T; Represa J; Klein R. 1995. Differential effects of combined trk receptor mutations on dorsal root ganglion and inner ear sensory neurons. Development 121(12):4067-75. [PubMed: 8575307]  [MGI Ref ID J:30344]

Moqrich A; Earley TJ; Watson J; Andahazy M; Backus C; Martin-Zanca D; Wright DE; Reichardt LF; Patapoutian A. 2004. Expressing TrkC from the TrkA locus causes a subset of dorsal root ganglia neurons to switch fate. Nat Neurosci 7(8):812-8. [PubMed: 15247919]  [MGI Ref ID J:92099]

Niu J; Vysochan A; Luo W. 2014. Dual innervation of neonatal Merkel cells in mouse touch domes. PLoS One 9(3):e92027. [PubMed: 24637732]  [MGI Ref ID J:215107]

Otal R; Martinez A; Soriano E. 2005. Lack of TrkB and TrkC signaling alters the synaptogenesis and maturation of mossy fiber terminals in the hippocampus. Cell Tissue Res 319(3):349-58. [PubMed: 15726425]  [MGI Ref ID J:105391]

Pinon LG; Minichiello L; Klein R; Davies AM. 1996. Timing of neuronal death in trkA, trkB and trkC mutant embryos reveals developmental changes in sensory neuron dependence on Trk signalling. Development 122(10):3255-61. [PubMed: 8898237]  [MGI Ref ID J:36236]

Raab M; Worl J; Brehmer A; Neuhuber WL. 2003. Reduction of NT-3 or TrkC results in fewer putative vagal mechanoreceptors in the mouse esophagus. Auton Neurosci 108(1-2):22-31. [PubMed: 14614961]  [MGI Ref ID J:102715]

Rice FL; Albers KM; Davis BM; Silos-Santiago I; Wilkinson GA; LeMaster AM; Ernfors P; Smeyne RJ; Aldskogius H; Phillips HS; Barbacid M; DeChiara TM; Yancopoulos GD; Dunne CE; Fundin BT. 1998. Differential dependency of unmyelinated and A delta epidermal and upper dermal innervation on neurotrophins, trk receptors, and p75LNGFR. Dev Biol 198(1):57-81. [PubMed: 9640332]  [MGI Ref ID J:107715]

Schimmang T; Alvarez-Bolado G; Minichiello L; Vazquez E; Giraldez F ; Klein R ; Represa J. 1997. Survival of inner ear sensory neurons in trk mutant mice. Mech Dev 64(1-2):77-85. [PubMed: 9232598]  [MGI Ref ID J:41896]

Schimmang T; Minichiello L; Vazquez E; San Jose I; Giraldez F; Klein R; Represa J. 1995. Developing inner ear sensory neurons require TrkB and TrkC receptors for innervation of their peripheral targets. Development 121(10):3381-91. [PubMed: 7588071]  [MGI Ref ID J:29245]

Sedy J; Szeder V; Walro JM; Ren ZG; Nanka O; Tessarollo L; Sieber-Blum M; Grim M; Kucera J. 2004. Pacinian corpuscle development involves multiple Trk signaling pathways. Dev Dyn 231(3):551-63. [PubMed: 15376326]  [MGI Ref ID J:93853]

Silos-Santiago I; Fagan AM; Garber M; Fritzsch B; Barbacid M. 1997. Severe sensory deficits but normal CNS development in newborn mice lacking TrkB and TrkC tyrosine protein kinase receptors. Eur J Neurosci 9(10):2045-56. [PubMed: 9421165]  [MGI Ref ID J:44795]

Spears N; Molinek MD; Robinson LL; Fulton N; Cameron H; Shimoda K; Telfer EE; Anderson RA; Price DJ. 2003. The role of neurotrophin receptors in female germ-cell survival in mouse and human. Development 130(22):5481-91. [PubMed: 14507777]  [MGI Ref ID J:85731]

Stenqvist A; Agerman K; Marmigere F; Minichiello L; Ernfors P. 2005. Genetic evidence for selective neurotrophin 3 signalling through TrkC but not TrkB in vivo. EMBO Rep 6(10):973-8. [PubMed: 16142215]  [MGI Ref ID J:101705]

de Carlos F; Cobo J; Germana G; Silos-Santiago I; Laura R; Haro JJ; Farinas I; Vega JA. 2006. Abnormal development of pacinian corpuscles in double trkB;trkC knockout mice. Neurosci Lett 410(3):157-61. [PubMed: 17101216]  [MGI Ref ID J:119011]

von Bohlen und Halbach O; Minichiello L; Unsicker K. 2005. Haploin-sufficiency for trkB and trkC receptors induces cell loss and accumulation of alpha-synuclein in the substantia nigra. FASEB J 19(12):1740-2. [PubMed: 16037097]  [MGI Ref ID J:102679]

von Bohlen und Halbach O; Minichiello L; Unsicker K. 2003. Haploinsufficiency in trkB and/or trkC neurotrophin receptors causes structural alterations in the aged hippocampus and amygdala. Eur J Neurosci 18(8):2319-25. [PubMed: 14622193]  [MGI Ref ID J:89676]

von Bohlen und Halbach O; Minichiello L; Unsicker K. 2008. TrkB but not trkC receptors are necessary for postnatal maintenance of hippocampal spines. Neurobiol Aging 29(8):1247-55. [PubMed: 17442456]  [MGI Ref ID J:140913]

Health & husbandry

The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Breeding & HusbandryWhen 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.

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2140.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

Pricing for International shipping destinations View USA Canada and Mexico Pricing

Cryopreserved

Cryopreserved Mice - Ready for Recovery

Price (US dollars $)
Cryorecovery* $2782.00
Animals Provided

At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Supply Notes

  • Cryorecovery - Standard.
    Progeny testing is not required.

    The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks. IMPORTANT NOTE: The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).

View USA Canada and Mexico Pricing View International Pricing

Standard Supply

Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.

Control Information

  Control
   Wild-type from the colony
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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