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 129S4/SvJae-Ntf5tm1Jae/J    (Changed: 07-SEP-06 ) Type Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Species laboratory mouse   Donating Investigator Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)

Appearance
white-bellied agouti
Related Genotype: A^w/A^w

Description
Mice homozygous for the targeted mutation are viable and fertile. Homozygous mutant mice lose sensory neurons in the nodose-petrosal and geniculate ganglia. However, they do not show loss of facial nucleus motor neurons, sympathetic neurons of the superior cervical ganglion, or dopaminergic neurons in the substantia nigra.

Development
This strain was developed in the lab of Dr. Rudolf Jaenisch at the Whitehead Institute for Biomedical Research at the Massachusetts Institute of Technology. A targeting vector containing neomycin resistance and phosphoglycerate kinase genes was used to disrupt the entire coding sequence. The construct was electroporated into 129S4/SvJae derived J1 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. The resulting chimeric animals were crossed to 129T1/Sv-p⁺ Tyr^c-ch Dnd1^Ter mice. The mice were then crossed to 129S1/SvImJ (Stock No. 2448) for cryopreservation.

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls

Additional Web Information

New 129 Nomenclature Bulletin

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI

- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested. Glaucoma 1, Open Angle, O; GLC1O   (NTF4)

View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Ntf5^tm1Jae/Ntf5^tm1Jae

        involves: 129S4/SvJae

• nervous system phenotype
• decreased neuron apoptosis
  • at E12 and E14, neuron apoptosis is reduced 74% and 65%, respectively, compared to in wild-type mice   (MGI Ref ID J:123022)
• decreased sensory neuron number
  • significant loss of all sensory neuron types in the nodose-petrosal, geniculate and L4 dorsal root ganglion in homozygous mice   (MGI Ref ID J:25566)
  • no difference in the number of facial motor neurons or superior cervical ganglion neurons is seen compared to controls   (MGI Ref ID J:25566)
  • no difference in the number of midbrain dopaminergic neurons is seen compared to controls   (MGI Ref ID J:25566)
• small L4 dorsal root ganglion
  • approximately 15% of the neurons are lost from the L4 DRG at two months of age   (MGI Ref ID J:25566)
• small geniculate ganglion
  • approximately half of the neurons are lost from the geniculate ganglion at E18.5   (MGI Ref ID J:25566)
• small nodose ganglion
  • greater than half of the neurons are lost from the nodose-petrosal ganglion at E18.5   (MGI Ref ID J:25566)
• small petrosal ganglion
  • greater than half of the neurons are lost from the nodose-petrosal ganglion at E18.5   (MGI Ref ID J:25566)
• small vestibular ganglion
  • approximately 20% of the neurons are lost from the vestibular ganglion   (MGI Ref ID J:25566)
• integument phenotype
• abnormal hair cycle
  • retarded catagen progression; follicles are still in early or middle catagen at time points when controls are in late catagen   (MGI Ref ID J:53271)
• thick skin
  • skin thicker than in controls   (MGI Ref ID J:53271)
• cellular phenotype
• decreased neuron apoptosis
  • at E12 and E14, neuron apoptosis is reduced 74% and 65%, respectively, compared to in wild-type mice   (MGI Ref ID J:123022)

View Research Applications

Research Applications

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

Ntf5^tm1Jae related

Apoptosis Research
Extracellular Modulators

Cancer Research
Growth Factors/Receptors/Cytokines

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

Neurobiology Research
Neurotrophic Factor Defects

Genes & Alleles

Gene & Allele Information provided by MGI

Allele Symbol		Ntf5tm1Jae
Allele Name		targeted mutation 1, Rudolf Jaenisch
Allele Type		Targeted (knock-out)
Common Name(s)		NT-4 -; NT4;
Mutation Made By		Dr. Rudolf Jaenisch,   Whitehead Institute (MIT)
Strain of Origin		129S4/SvJae
ES Cell Line Name		J1
ES Cell Line Strain		129S4/SvJae
Gene Symbol and Name		Ntf5, neurotrophin 5
Chromosome		7
Gene Common Name(s)		2900040K06Rik; AI462899; GLC10; GLC1O; NT-4; NT-4/5; NT-5; NT4; NT4/5; NT4P; NT5; Ntf-5; Ntf4; RIKEN cDNA 2900040K06 gene; expressed sequence AI462899; neurotrophin 4; neurotrophin-4;
Molecular Note		The entire coding region of the gene was replaced by a PGK-neomycin cassette. [MGI Ref ID J:25566]

Genotyping

Genotyping Information

Genotyping Protocols

Ntf5^tm1Jae, Standard PCR

Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Liu X; Ernfors P; Wu H; Jaenisch R. 1995. Sensory but not motor neuron deficits in mice lacking NT4 and BDNF. Nature 375(6528):238-41. [PubMed: 7746325]  [MGI Ref ID J:25566]

Additional References

Fox EA; Phillips RJ; Baronowsky EA; Byerly MS; Jones S; Powley TL. 2001. Neurotrophin-4 deficient mice have a loss of vagal intraganglionic mechanoreceptors from the small intestine and a disruption of short-term satiety. J Neurosci 21(21):8602-15. [PubMed: 11606648]  [MGI Ref ID J:72356]

Stucky CL; Shin JB; Lewin GR. 2002. Neurotrophin-4: a survival factor for adult sensory neurons. Curr Biol 12(16):1401-4. [PubMed: 12194821]  [MGI Ref ID J:78592]

Ntf5^tm1Jae related

Agerman K; Baudet C; Fundin B; Willson C; Ernfors P. 2000. Attenuation of a caspase-3 dependent cell death in NT4- and p75-deficient embryonic sensory neurons. Mol Cell Neurosci 16(3):258-68. [PubMed: 10995552]  [MGI Ref ID J:123022]

Botchkarev VA; Botchkareva NV; Welker P; Metz M; Lewin GR; Subramaniam A; Bulfone-Paus S; Hagen E; Braun A; Lommatzsch M; Renz H; Paus AR. 1999. A new role for neurotrophins: involvement of brain-derived neurotrophic factor and neurotrophin-4 in hair cycle control. FASEB J 13(2):395-410. [PubMed: 9973328]  [MGI Ref ID J:53271]

Botchkarev VA; Metz M; Botchkareva NV; Welker P; Lommatzsch M; Renz H; Paus R. 1999. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 act as epitheliotrophins in murine skin. Lab Invest 79(5):557-72. [PubMed: 10334567]  [MGI Ref ID J:54992]

Byerly MS; Fox EA. 2006. High-fat hyperphagia in neurotrophin-4 deficient mice reveals potential role of vagal intestinal sensory innervation in long-term controls of food intake. Neurosci Lett 400(3):240-5. [PubMed: 16530962]  [MGI Ref ID J:111211]

Calamusa M; Pattabiraman PP; Pozdeyev N; Iuvone PM; Cellerino A; Domenici L. 2007. Specific alterations of tyrosine hydroxylase immunopositive cells in the retina of NT-4 knock out mice. Vision Res 47(11):1523-36. [PubMed: 17350071]  [MGI Ref ID J:124475]

Chi MM; Powley TL. 2007. NT-4-deficient mice lack sensitivity to meal-associated preabsorptive feedback from lipids. Am J Physiol Regul Integr Comp Physiol 292(6):R2124-35. [PubMed: 17303678]  [MGI Ref ID J:143021]

ElShamy WM; Ernfors P. 1997. Brain-derived neurotrophic factor, neurotrophin-3, and neurotrophin-4 complement and cooperate with each other sequentially during visceral neuron development. J Neurosci 17(22):8667-75. [PubMed: 9348335]  [MGI Ref ID J:44086]

Endres M; Fan G; Hirt L; Fujii M; Matsushita K; Liu X; Jaenisch R; Moskowitz MA. 2000. Ischemic brain damage in mice after selectively modifying BDNF or NT4 gene expression. J Cereb Blood Flow Metab 20(1):139-44. [PubMed: 10616802]  [MGI Ref ID J:60087]

English AW; Cucoranu D; Mulligan A; Rodriguez JA; Sabatier MJ. 2011. Neurotrophin-4/5 is implicated in the enhancement of axon regeneration produced by treadmill training following peripheral nerve injury. Eur J Neurosci 33(12):2265-71. [PubMed: 21623957]  [MGI Ref ID J:176369]

English AW; Meador W; Carrasco DI. 2005. Neurotrophin-4/5 is required for the early growth of regenerating axons in peripheral nerves. Eur J Neurosci 21(10):2624-34. [PubMed: 15926911]  [MGI Ref ID J:101068]

Fan G; Copray S; Huang EJ; Jones K; Yan Q; Walro J; Jaenisch R; Kucera J. 2000. Formation of a full complement of cranial proprioceptors requires multiple neurotrophins. Dev Dyn 218(2):359-70. [PubMed: 10842362]  [MGI Ref ID J:62766]

Fox EA; Phillips RJ; Baronowsky EA; Byerly MS; Jones S; Powley TL. 2001. Neurotrophin-4 deficient mice have a loss of vagal intraganglionic mechanoreceptors from the small intestine and a disruption of short-term satiety. J Neurosci 21(21):8602-15. [PubMed: 11606648]  [MGI Ref ID J:72356]

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]

Gacek RR; Khetarpal U. 1998. Neurotrophin 3, not brain-derived neurotrophic factor or neurotrophin 4, knockout mice have delay in vestibular compensation after unilateral labyrinthectomy. Laryngoscope 108(5):671-8. [PubMed: 9591544]  [MGI Ref ID J:113175]

He XP; Butler L; Liu X; McNamara JO. 2006. The tyrosine receptor kinase B ligand, neurotrophin-4, is not required for either epileptogenesis or tyrosine receptor kinase B activation in the kindling model. Neuroscience 141(1):515-20. [PubMed: 16650613]  [MGI Ref ID J:110287]

Heppenstall PA; Lewin GR. 2001. BDNF but not NT-4 is required for normal flexion reflex plasticity and function. Proc Natl Acad Sci U S A 98(14):8107-12. [PubMed: 11438749]  [MGI Ref ID J:126994]

Huang T; Krimm RF. 2010. Developmental expression of Bdnf, Ntf4/5, and TrkB in the mouse peripheral taste system. Dev Dyn 239(10):2637-46. [PubMed: 21038447]  [MGI Ref ID J:165547]

Liu X; Jaenisch R. 2000. Severe peripheral sensory neuron loss and modest motor neuron reduction in mice with combined deficiency of brain-derived neurotrophic factor, neurotrophin 3 and neurotrophin 4/5. Dev Dyn 218(1):94-101. [PubMed: 10822262]  [MGI Ref ID J:62072]

Lucas G; Hendolin P; Harkany T; Agerman K; Paratcha G; Holmgren C; Zilberter Y; Sairanen M; Minichiello L; Castren E; Ernfors P. 2003. Neurotrophin-4 mediated TrkB activation reinforces morphine-induced analgesia. Nat Neurosci 6(3):221-2. [PubMed: 12601381]  [MGI Ref ID J:109298]

McIlwrath SL; Hu J; Anirudhan G; Shin JB; Lewin GR. 2005. The sensory mechanotransduction ion channel ASIC2 (acid sensitive ion channel 2) is regulated by neurotrophin availability. Neuroscience 131(2):499-511. [PubMed: 15708491]  [MGI Ref ID J:105150]

Patel AV; Huang T; Krimm RF. 2010. Lingual and palatal gustatory afferents each depend on both BDNF and NT-4, but the dependence is greater for lingual than palatal afferents. J Comp Neurol 518(16):3290-301. [PubMed: 20575060]  [MGI Ref ID J:177759]

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]

Roosen A; Schober A; Strelau J; Bottner M; Faulhaber J; Bendner G; McIlwrath SL; Seller H; Ehmke H; Lewin GR; Unsicker K. 2001. Lack of neurotrophin-4 causes selective structural and chemical deficits in sympathetic ganglia and their preganglionic innervation. J Neurosci 21(9):3073-84. [PubMed: 11312292]  [MGI Ref ID J:109465]

Royo NC; Conte V; Saatman KE; Shimizu S; Belfield CM; Soltesz KM; Davis JE; Fujimoto ST; McIntosh TK. 2006. Hippocampal vulnerability following traumatic brain injury: a potential role for neurotrophin-4/5 in pyramidal cell neuroprotection. Eur J Neurosci 23(5):1089-102. [PubMed: 16553773]  [MGI Ref ID J:107158]

Schober A; Wolf N; Huber K; Hertel R; Krieglstein K; Minichiello L; Kahane N; Widenfalk J; Kalcheim C; Olson L; Klein R; Lewin GR; Unsicker K. 1998. TrkB and neurotrophin-4 are important for development and maintenance of sympathetic preganglionic neurons innervating the adrenal medulla. J Neurosci 18(18):7272-84. [PubMed: 9736648]  [MGI Ref ID J:120428]

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]

Smith DJ; Leil TA; Liu X. 2003. Neurotrophin-4 is required for tolerance to morphine in the mouse. Neurosci Lett 340(2):103-6. [PubMed: 12668247]  [MGI Ref ID J:107939]

Stucky CL; Shin JB; Lewin GR. 2002. Neurotrophin-4: a survival factor for adult sensory neurons. Curr Biol 12(16):1401-4. [PubMed: 12194821]  [MGI Ref ID J:78592]

Xie CW; Sayah D; Chen QS; Wei WZ; Smith D; Liu X. 2000. Deficient long-term memory and long-lasting long-term potentiation in mice with a targeted deletion of neurotrophin-4 gene. Proc Natl Acad Sci U S A 97(14):8116-21. [PubMed: 10869436]  [MGI Ref ID J:63270]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

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

Colony Maintenance

Diet Information	LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls

General Supply Notes

• Genomic DNA is available for this strain from the Mouse DNA Resource.

Control Information

	Control
	002448 129S1/SvImJ	(approximate)
Considerations for Choosing Controls
Control Pricing Information for Genetically Engineered Mutant Strains.

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The Jackson Laboratory's Genotype Promise

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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