Targeted Mutation in the Neurotrophin-3 Gene Results in Loss of Muscle Sensory Neurons

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1994 Dec 6

PMID 7991545

Citations 68

Authors

L Tessarollo

K S Vogel

M E Palko

S W Reid

L F Parada

Affiliations

Soon will be listed here.

Abstract

Neurotrophin 3 (NT-3) is one of four related polypeptide growth factors that share structural and functional homology to nerve growth factor (NGF). NT-3 and its receptor, called neurotrophic tyrosine kinase receptor type 3 (Ntrk3; also called TrkC), are expressed early and throughout embryogenesis. We have inactivated the NT-3 gene in embryonic stem (ES) cells by homologous recombination. The mutated allele has been transmitted through the mouse germ line, and heterozygote intercrosses have yielded homozygous mutant newborn pups. The NT-3-deficient mutants fail to thrive and exhibit severe neurological dysfunction. Analysis of mutant embryos uncovers loss of Ntrk3/TrkC-expressing sensory neurons and abnormalities at early stages of sensory neuronal development. NT-3-deficient mice will permit further study of the role of this neurotrophin in neural development.

Citing Articles

Search for unknown neural link between the masticatory and cognitive brain systems to clarify the involvement of its impairment in the pathogenesis of Alzheimer's disease.

Kang Y, Toyoda H, Saito M Front Cell Neurosci. 2024; 18:1425645.

PMID: 38994328 PMC: 11236757. DOI: 10.3389/fncel.2024.1425645.

Effects of Whole-Body Vibration and Manually Assisted Locomotor Therapy on Neurotrophin-3 Expression and Microglia/Macrophage Mobilization Following Thoracic Spinal Cord Injury in Rats.

Schaufler D, Manthou M, Theotokis P, Rink-Notzon S, Angelov D Curr Issues Mol Biol. 2023; 45(4):3238-3254.

PMID: 37185735 PMC: 10137282. DOI: 10.3390/cimb45040211.

Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site.

Jing Y, Bai F, Wang L, Yang D, Yan Y, Wang Q Microbiol Spectr. 2022; 10(3):e0017722.

PMID: 35467388 PMC: 9241636. DOI: 10.1128/spectrum.00177-22.

Innervation in organogenesis.

Honeycutt S, NGuetta P, OBrien L Curr Top Dev Biol. 2022; 148:195-235.

PMID: 35461566 PMC: 10636594. DOI: 10.1016/bs.ctdb.2022.02.004.

The Prevailing Role of Topoisomerase 2 Beta and its Associated Genes in Neurons.

Neha S , Dholaniya P Mol Neurobiol. 2021; 58(12):6443-6459.

PMID: 34546528 DOI: 10.1007/s12035-021-02561-0.

References

Korsching S . The neurotrophic factor concept: a reexamination. J Neurosci. 1993; 13(7):2739-48. PMC: 6576699. View

Farinas I, Jones K, Backus C, Wang X, Reichardt L . Severe sensory and sympathetic deficits in mice lacking neurotrophin-3. Nature. 1994; 369(6482):658-61. DOI: 10.1038/369658a0. View

Barres B, Schmid R, Sendnter M, Raff M . Multiple extracellular signals are required for long-term oligodendrocyte survival. Development. 1993; 118(1):283-95. DOI: 10.1242/dev.118.1.283. View

Klein R, Smeyne R, Wurst W, Long L, Auerbach B, Joyner A . Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death. Cell. 1993; 75(1):113-22. View

Tessarollo L, Tsoulfas P, Gilbert D, Jenkins N, Copeland N, Parada L . trkC, a receptor for neurotrophin-3, is widely expressed in the developing nervous system and in non-neuronal tissues. Development. 1993; 118(2):463-75. DOI: 10.1242/dev.118.2.463. View

Swiatek P, Gridley T . Perinatal lethality and defects in hindbrain development in mice homozygous for a targeted mutation of the zinc finger gene Krox20. Genes Dev. 1993; 7(11):2071-84. DOI: 10.1101/gad.7.11.2071. View

Levi-Montalcini R . The nerve growth factor 35 years later. Science. 1987; 237(4819):1154-62. DOI: 10.1126/science.3306916. View

Maisonpierre P, Belluscio L, Squinto S, Ip N, Furth M, Lindsay R . Neurotrophin-3: a neurotrophic factor related to NGF and BDNF. Science. 1990; 247(4949 Pt 1):1446-51. DOI: 10.1126/science.247.4949.1446. View

Barbacid M, Parada L . Expression of the trk proto-oncogene is restricted to the sensory cranial and spinal ganglia of neural crest origin in mouse development. Genes Dev. 1990; 4(5):683-94. DOI: 10.1101/gad.4.5.683. View

10.

Soriano P, Montgomery C, Geske R, Bradley A . Targeted disruption of the c-src proto-oncogene leads to osteopetrosis in mice. Cell. 1991; 64(4):693-702. DOI: 10.1016/0092-8674(91)90499-o. View

11.

Squinto S, Stitt T, Aldrich T, Davis S, Blanco S, Radziejewski C . trkB encodes a functional receptor for brain-derived neurotrophic factor and neurotrophin-3 but not nerve growth factor. Cell. 1991; 65(5):885-893. DOI: 10.1016/0092-8674(91)90395-F. View

12.

Soppet D, Escandon E, Maragos J, Middlemas D, Reid S, Blair J . The neurotrophic factors brain-derived neurotrophic factor and neurotrophin-3 are ligands for the trkB tyrosine kinase receptor. Cell. 1991; 65(5):895-903. DOI: 10.1016/0092-8674(91)90396-g. View

13.

Cordon-Cardo C, Tapley P, Jing S, Nanduri V, ORourke E, Lamballe F . The trk tyrosine protein kinase mediates the mitogenic properties of nerve growth factor and neurotrophin-3. Cell. 1991; 66(1):173-83. PMC: 2711891. DOI: 10.1016/0092-8674(91)90149-s. View

14.

Klein R, Nanduri V, Jing S, Lamballe F, Tapley P, Bryant S . The trkB tyrosine protein kinase is a receptor for brain-derived neurotrophic factor and neurotrophin-3. Cell. 1991; 66(2):395-403. PMC: 2710095. DOI: 10.1016/0092-8674(91)90628-c. View

15.

Lamballe F, Klein R, Barbacid M . trkC, a new member of the trk family of tyrosine protein kinases, is a receptor for neurotrophin-3. Cell. 1991; 66(5):967-79. DOI: 10.1016/0092-8674(91)90442-2. View

16.

Berkemeier L, Winslow J, Kaplan D, Nikolics K, Goeddel D, Rosenthal A . Neurotrophin-5: a novel neurotrophic factor that activates trk and trkB. Neuron. 1991; 7(5):857-66. DOI: 10.1016/0896-6273(91)90287-a. View

17.

Barde Y . The nerve growth factor family. Prog Growth Factor Res. 1990; 2(4):237-48. DOI: 10.1016/0955-2235(90)90021-b. View

18.

Kalcheim C, Carmeli C, Rosenthal A . Neurotrophin 3 is a mitogen for cultured neural crest cells. Proc Natl Acad Sci U S A. 1992; 89(5):1661-5. PMC: 48512. DOI: 10.1073/pnas.89.5.1661. View

19.

Ruit K, ELLIOTT J, Osborne P, Yan Q, Snider W . Selective dependence of mammalian dorsal root ganglion neurons on nerve growth factor during embryonic development. Neuron. 1992; 8(3):573-87. DOI: 10.1016/0896-6273(92)90284-k. View

20.

Ip N, Ibanez C, Nye S, McClain J, Jones P, Gies D . Mammalian neurotrophin-4: structure, chromosomal localization, tissue distribution, and receptor specificity. Proc Natl Acad Sci U S A. 1992; 89(7):3060-4. PMC: 48803. DOI: 10.1073/pnas.89.7.3060. View