TARGETED MUTATION IN THE NEUROTROPHIN-3 GENE RESULTS IN LOSS OF MUSCLE SENSORY NEURONS
TARGETED MUTATION IN THE NEUROTROPHIN-3 GENE RESULTS IN LOSS OF MUSCLE SENSORY NEURONS
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DOI：
10.1073/pnas.91.25.11844
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发表时间：
1994-12-06
影响因子：
11.1
通讯作者：
PARADA, LF
中科院分区：
文献类型：
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作者：
TESSAROLLO, L;VOGEL, KS;PARADA, LF
神经营养因子3 （NT-3）是与神经生长因子（NGF）具有结构和功能同源性的四种相关多肽生长因子之一。NT-3及其受体，称为神经营养酪氨酸激酶受体3型（Ntrk3；也称为TrkC），在胚胎发生早期和整个过程中表达。我们用同源重组法灭活了胚胎干细胞的NT-3基因。突变的等位基因通过小鼠生殖系传播，杂合子交叉产生纯合子突变的新生幼崽。缺乏nt3的突变体不能茁壮成长，并表现出严重的神经功能障碍。突变胚胎的分析揭示了表达Ntrk3/ trkc的感觉神经元的缺失和感觉神经元发育早期阶段的异常。nt3缺陷小鼠将允许进一步研究这种神经营养因子在神经发育中的作用。
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 NT3-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. NT3-deficient mice will permit further study of the role of this neurotrophin in neural development.