Resibois A, Cuvelier L, Goffinet A M
Laboratoire d'Histologie, Faculté de Médecine, Université Libre de Bruxelles, Brussels, Belgium.
Neuroscience. 1997 Sep;80(1):175-90. doi: 10.1016/s0306-4522(97)00009-2.
The lurcher mutation induces Purkinje cell degeneration in heterozygous mice, and neonatal death in homozygous animals. Using the D6Mit16 Simple Sequence Length Polymorphic marker in F2 hybrids between AKR +/+ mice and B6+/Lc mice, homozygous lurcher fetuses and newborns as well as heterozygous and normal littermates were identified, and their brain morphology was analysed. In homozygous lurcher embryos at embryonic day 18 and neonates the cerebellum was hypotrophic, particularly in the posterior half. Purkinje cells were smaller in the whole cerebellum and showed a maturational delay. Calretinin-positive cells were less frequently observed in the depth of the vermis than in normal mice. Both Purkinje cells and the vermal calretinin-positive cells were more abnormal in fetuses at day 19 and newborn mutants than one day earlier. An abnormal number of pycnotic cells were observed in the cerebellum, especially in newborn mutants. Brainstem abnormalities were characterized by abnormal curvature, caudal displacement of the pontine gray nuclei which were located caudally along the ventral border of the superior olivary complex, a drastic decrease in Purkinje cell axons in all the vestibular nuclei and the presence of dystrophic processes in at least two calbindin-positive cell groups of the dorsal pontine region. These results show that the mutation, which is semidominant in Purkinje cells, is recessive in other cell groups of the cerebellum and brainstem. They reveal that the sequence leading to Purkinje cell death appears to be similar in homozygous and heterozygous mice, although occurring earlier and worsening more quickly in the former. Lastly, they confirm the absence of effect of the mutation on the neurons of the inferior olivary complex.
“蹒跚者”突变会导致杂合子小鼠的浦肯野细胞退化，以及纯合子动物的新生儿死亡。利用 D6Mit16 简单序列长度多态性标记，在 AKR +/+ 小鼠和 B6+/Lc 小鼠的 F2 杂交后代中，鉴定出纯合“蹒跚者”胎儿和新生儿以及杂合子和正常同窝小鼠，并分析了它们的脑形态。在胚胎第 18 天的纯合“蹒跚者”胚胎和新生儿中，小脑发育不良，尤其是后半部分。整个小脑中的浦肯野细胞较小，且显示出成熟延迟。与正常小鼠相比，在蚓部深处较少观察到钙视网膜蛋白阳性细胞。在第 19 天的胎儿和新生突变体中，浦肯野细胞和蚓部钙视网膜蛋白阳性细胞比早一天时更异常。在小脑中观察到异常数量的固缩细胞，尤其是在新生突变体中。脑干异常的特征为异常弯曲、脑桥灰质核尾侧移位，脑桥灰质核沿着上橄榄复合体腹侧边界位于尾侧，所有前庭核中浦肯野细胞轴突急剧减少，以及脑桥背侧区域至少两个钙结合蛋白阳性细胞群中出现营养不良性改变。这些结果表明，该突变在浦肯野细胞中是半显性的，但在小脑和脑干的其他细胞群中是隐性的。它们揭示，导致浦肯野细胞死亡的序列在纯合子和杂合子小鼠中似乎相似，尽管在前者中出现得更早且恶化得更快。最后，它们证实该突变对下橄榄复合体的神经元没有影响。
