Hadj-Sahraoui N, Frédéric F, Delhaye-Bouchaud N, Mariani J
Laboratoire de Neurobiologie du Développement, Institut des Neurosciences (CNRS URA 1488), Université Pierre et Marie Curie, Paris, France.
J Neurogenet. 1996 Dec;11(1-2):45-58. doi: 10.3109/01677069609107062.
Homozygous mutant mice such as staggerer (sg/sg) or reeler (rl/rl) exhibit a marked ataxia associated with an atrophic cerebellum during the first postnatal weeks and a reduced number of Purkinje cells, the deficit reaching about 75% in sg/sg and 50% in rl/rl as compared to age- and sex-matched mice from the same strain background. These two mutations are classically viewed as recessive, but we have recently shown that heterozygous staggerer (+/sg) mice exhibit a progressive and age-related loss of Purkinje cells between 3 and 12 months of age, despite their apparent clinical normality (Shojaeian-Zanjani et al., 1992). In the present study, we have investigated whether a similar cell loss exists in the cerebellum of heterozygous +/rl mice. The number of Purkinje cells was counted in serial parasagittal sections of the cerebellum of +/rl and their +/+ littermates at 3, 16 and 26 months of age. Our results reveal a 16% deficit in the number of Purkinje cells in 3-month-old +/rl and a 24% one in 16-month-old animals: surprisingly this deficit is only present in the +/rl males, while the females are spared. These results suggest that the reeler gene (D'Arcangelo et al., 1995) exerts its effect on Purkinje cell number in a gender-specific fashion in heterozygous mutant mice.
纯合突变小鼠，如蹒跚者（sg/sg）或旋转者（rl/rl），在出生后的头几周表现出明显的共济失调，伴有小脑萎缩，浦肯野细胞数量减少。与来自相同品系背景、年龄和性别匹配的小鼠相比，sg/sg小鼠的浦肯野细胞数量减少约75%，rl/rl小鼠减少约50%。这两种突变传统上被视为隐性突变，但我们最近发现，杂合蹒跚者（+/sg）小鼠在3至12个月大时，尽管其临床症状看似正常，但仍会出现浦肯野细胞的渐进性和与年龄相关的丢失（Shojaeian-Zanjani等人，1992年）。在本研究中，我们调查了杂合+/rl小鼠的小脑中是否存在类似的细胞丢失。在3、16和26个月大时，对+/rl小鼠及其+/+同窝小鼠小脑的连续矢状旁切片中的浦肯野细胞数量进行了计数。我们的结果显示，3个月大的+/rl小鼠浦肯野细胞数量减少了16%，16个月大的动物减少了24%：令人惊讶的是，这种减少仅存在于+/rl雄性小鼠中，而雌性小鼠则未受影响。这些结果表明，旋转者基因（D'Arcangelo等人，1995年）在杂合突变小鼠中以性别特异性方式对浦肯野细胞数量产生影响。
