Klein R, Smeyne R J, Wurst W, Long L K, Auerbach B A, Joyner A L, Barbacid M
Department of Molecular Biology, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08543-4000.
Cell. 1993 Oct 8;75(1):113-22.
We have generated mice carrying a germline mutation in the tyrosine kinase catalytic domain of the trkB gene. This mutation eliminates expression of gp145trkB, a protein-tyrosine kinase that serves as the signaling receptor for two members of the nerve growth factor family of neurotrophins, brain-derived neurotrophic factor and neurotrophin-4. Mice homozygous for this mutation, trkBTK(-/-), develop to birth. However, these animals do not display feeding activity, and most die by P1. Neuroanatomical examination of trkBTK (-/-) mice revealed neuronal deficiencies in the central (facial motor nucleus and spinal cord) and peripheral (trigeminal and dorsal root ganglia) nervous systems. These findings illustrate the role of the gp145trkB protein-tyrosine kinase receptor in the ontogeny of the mammalian nervous system.
我们培育出了在trkB基因的酪氨酸激酶催化结构域携带种系突变的小鼠。这种突变消除了gp145trkB的表达，gp145trkB是一种蛋白质酪氨酸激酶，作为神经营养因子神经生长因子家族的两个成员——脑源性神经营养因子和神经营养因子-4的信号受体。这种突变的纯合子小鼠trkBTK(-/-)能发育到出生。然而，这些动物不表现出进食活动，大多数在出生后第1天死亡。对trkBTK(-/-)小鼠的神经解剖学检查显示，其在中枢（面神经运动核和脊髓）和外周（三叉神经节和背根神经节）神经系统存在神经元缺陷。这些发现阐明了gp145trkB蛋白质酪氨酸激酶受体在哺乳动物神经系统个体发育中的作用。
