Bayer S A, Wills K V, Triarhou L C, Verina T, Thomas J D, Ghetti B
Department of Biology, Indiana-Purdue University, Indianapolis 46202-5132, USA.
Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9137-40. doi: 10.1073/pnas.92.20.9137.
In homozygous weaver (wv/wv) mutant mice, nearly 50% of the dopaminergic substantia nigra neurons degenerate by postnatal day 20. We have now determined that the total number of dopaminergic neurons in the ventral midbrains of a litter of obligatory homozygous weaver pups and a litter of normal wild-type control pups indicates that no significant differences are present between groups at birth. To test the hypothesis that the subsequent degeneration of these neurons is linked to their time of origin, [3H]thymidine autoradiography was combined with tyrosine hydroxylase immunocytochemistry to construct neurogenetic timetables on postnatal day 20 in wild-type mice and weaver homozygotes. Both groups have the same span of neurogenesis but have statistically different proportions of neurons generated on specific days. In wild-type mice, more than half of the dopaminergic neurons originate on or after embryonic day 12. In contrast, over two-thirds of the surviving dopaminergic neurons in homozygous weaver mice originate on or before embryonic day 11. Our data suggest that the weaver gene does not interfere with the generation of dopaminergic neurons, but it preferentially kills late-generated dopaminergic neurons between birth and postnatal day 20.
在纯合织工（wv/wv）突变小鼠中，近50%的多巴胺能黑质神经元在出生后第20天退化。我们现已确定，一窝纯合织工幼崽和一窝正常野生型对照幼崽腹侧中脑中多巴胺能神经元的总数表明，两组在出生时没有显著差异。为了检验这些神经元随后的退化与其起源时间有关的假设，将[3H]胸腺嘧啶放射自显影与酪氨酸羟化酶免疫细胞化学相结合，以构建野生型小鼠和织工纯合子出生后第20天的神经发生时间表。两组的神经发生跨度相同，但在特定日期产生的神经元比例在统计学上有所不同。在野生型小鼠中，超过一半的多巴胺能神经元起源于胚胎第12天或之后。相比之下，纯合织工小鼠中存活的多巴胺能神经元中，超过三分之二起源于胚胎第11天或之前。我们的数据表明，织工基因不会干扰多巴胺能神经元的产生，但它会在出生至出生后第20天期间优先杀死晚期产生的多巴胺能神经元。
