Jones K R, Fariñas I, Backus C, Reichardt L F
Howard Hughes Medical Institute University of California, San Francisco School of Medicine 94143.
Cell. 1994 Mar 25;76(6):989-99. doi: 10.1016/0092-8674(94)90377-8.
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.
脑源性神经营养因子(BDNF)是一种神经营养素,在体外可增强几类神经元的存活和分化。为了确定其基本功能,我们对BDNF基因进行了突变。大多数纯合突变体在出生后2天内死亡,但有一部分能存活2至4周。这些突变体出现神经系统功能障碍症状,包括共济失调。BDNF突变纯合子的颅神经和脊髓感觉神经元数量大幅减少。尽管它们的中枢神经系统没有明显的结构异常,但许多神经元中神经肽Y和钙结合蛋白的表达发生了改变,这表明它们的功能不正常。与缺乏BDNF受体TrkB的小鼠不同,BDNF突变体中的运动神经元看起来正常。