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PMID: 8137432 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Targeted disruption of the BDNF gene perturbs brain and sensory neuron development but not motor neuron development.

Cell ·Vol. 76 ·No. 6 ·1994-03-25 ·Pages 989-99

Jones KR, Fariñas I, Backus C, Reichardt LF

Abstract

Brain-derived neurotrophic factor (BDNF), a neurotrophin, enhances the survival and differentiation of several classes of neurons in vitro. To determine its essential functions, we have mutated the BDNF gene. Most homozygote mutants die within 2 days after birth, but a fraction live for 2-4 weeks. These develop symptoms of nervous system dysfunction, including ataxia. The BDNF mutant homozygotes have substantially reduced numbers of cranial and spinal sensory neurons. Although their central nervous systems show no gross structural abnormalities, expression of neuropeptide Y and calcium-binding proteins is altered in many neurons, suggesting they do not function normally. In contrast with mice lacking the BDNF receptor TrkB, motor neurons appear normal in the BDNF mutant.

Related Genes
BDNF
MeSH Terms
Animals Brain/cytology,growth & development Brain-Derived Neurotrophic Factor Calcium-Binding Proteins/biosynthesis Cell Division/physiology Cell Line Female Male Mice Mice, Inbred C57BL Mice, Mutant Strains Motor Neurons/physiology Mutation Nerve Growth Factors/genetics,physiology Nerve Tissue Proteins/genetics,physiology Neurons, Afferent/physiology Sequence Deletion
Chemicals
Brain-Derived Neurotrophic Factor Calcium-Binding Proteins Nerve Growth Factors Nerve Tissue Proteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Jones K R
Howard Hughes Medical Institute University of California, San Francisco School of Medicine 94143.
Fariñas I
Backus C
Reichardt L F
References (21)
21 references, click to expand
  1. The neurotrophic factor concept: a reexamination.
    J Neurosci. 1993 Jul;13(7):2739-48 PMID: 8331370
  2. Cultured hippocampal neurons show responses to BDNF, NT-3, and NT-4, but not NGF.
    J Neurosci. 1993 Aug;13(8):3394-405 PMID: 7688038
  3. Targeted disruption of the trkB neurotrophin receptor gene results in nervous system lesions and neonatal death.
    Cell. 1993 Oct 8;75(1):113-22 PMID: 8402890
  4. Staining for nerve fiber and cholinesterase activity in fresh frozen sections.
    Am J Clin Pathol. 1967 Jan;47(1):74-7 PMID: 4163073
  5. An immunochemical analysis of the distribution of a brain-specific polypeptide, PEP-19.
    J Neurochem. 1988 Dec;51(6):1771-6 PMID: 3183658
  6. Molecular cloning and expression of brain-derived neurotrophic factor.
    Nature. 1989 Sep 14;341(6238):149-52 PMID: 2779653
  7. Regional distribution of brain-derived neurotrophic factor mRNA in the adult mouse brain.
    EMBO J. 1990 Aug;9(8):2459-64 PMID: 2369898
  8. Calbindin D-28k and parvalbumin in the rat nervous system.
    Neuroscience. 1990;35(2):375-475 PMID: 2199841
  9. Molecular cloning of a human gene that is a member of the nerve growth factor family.
    Proc Natl Acad Sci U S A. 1990 Oct;87(20):8060-4 PMID: 2236018
  10. Evidence that biological activity of NGF is mediated through a novel subclass of high affinity receptors.
    Neuron. 1991 Apr;6(4):649-63 PMID: 1849725
  11. Two conserved domains in the NGF propeptide are necessary and sufficient for the biosynthesis of correctly processed and biologically active NGF.
    EMBO J. 1991 Sep;10(9):2395-400 PMID: 1868828
  12. New protein fold revealed by a 2.3-A resolution crystal structure of nerve growth factor.
    Nature. 1991 Dec 5;354(6352):411-4 PMID: 1956407
  13. Disruption of the low affinity receptor-binding site in NGF allows neuronal survival and differentiation by binding to the trk gene product.
    Cell. 1992 Apr 17;69(2):329-41 PMID: 1314703
  14. Novel roles for neurotrophins are suggested by BDNF and NT-3 mRNA expression in developing neurons.
    Neuron. 1992 Sep;9(3):449-63 PMID: 1345671
  15. Neurotrophin receptors: a window into neuronal differentiation.
    Neuron. 1992 Oct;9(4):583-93 PMID: 1327010
  16. Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia.
    Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9915-9 PMID: 1409719
  17. Calcium-binding proteins in the nervous system.
    Trends Neurosci. 1992 Aug;15(8):303-8 PMID: 1384200
  18. Regulation of neuropeptide expression in cultured cerebral cortical neurons by brain-derived neurotrophic factor.
    J Neurochem. 1993 Feb;60(2):772-5 PMID: 8093484
  19. Molecular cloning of rat trkC and distribution of cells expressing messenger RNAs for members of the trk family in the rat central nervous system.
    Neuroscience. 1992 Dec;51(3):513-32 PMID: 1488112
  20. Similarities and differences in the way neurotrophins interact with the Trk receptors in neuronal and nonneuronal cells.
    Neuron. 1993 Feb;10(2):137-49 PMID: 7679912
  21. An extended surface of binding to Trk tyrosine kinase receptors in NGF and BDNF allows the engineering of a multifunctional pan-neurotrophin.
    EMBO J. 1993 Jun;12(6):2281-93 PMID: 8508763
Article Info
Journal
Cell
Abbr.
Cell
ISSN
0092-8674
DOI
10.1016/0092-8674(94)90377-8
Published
1994-03-25
Pages
989-99
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2711896
Subset
IM
Grants
NINDS NIH HHS · P01 NS016033 · United States
NINDS NIH HHS · P01 NS016033-17A10014 · United States
NIMH NIH HHS · MH48200 · United States
External Links
PubMed source DOI: 10.1016/0092-8674(94)90377-8 PMC Full Text View journal details
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