Goldowitz D, Mullen R J
J Neurosci. 1982 Oct;2(10):1474-85. doi: 10.1523/JNEUROSCI.02-10-01474.1982.
Experimental mouse chimeras were used to determine the site(s) of gene action in the weaver mutant cerebellum. Chimeras containing mixtures of heterozygous weaver (wv/+) and non-weaver (+/+) cells were produced by the standard embryo aggregation technique. The non-weaver component of the chimera was chosen so that Purkinje cells or granule cells could be distinguished histologically from weaver Purkinje or granule cells. Levels of beta-glucuronidase activity were used to mark Purkinje cells, with the weaver strain having a high beta-glucuronidase activity, while the non-weaver strain had low beta-glucuronidase activity. The increased centralized clumping of heterochromatin in ichthyosis (ic) mutant mice compared to non-ic mice was used to mark granule cell populations. In the weaver chimera, there was a decreased cerebellar size, decreased numbers of Purkinje and granule cells, and increased ectopic Purkinje and granule cells compared to non-weaver, control mice. With the glucuronidase cell marker, it was found that there was no correlation between ectopia and genotype; that is, genetically normal cells, as well as weaver cells, were found in ectopic positions. Thus, the weaver gene acts extrinsic to the Purkinje cells in creating the ectopia characteristic of heterozygous weaver mutants. Analysis of the ectopic granule cells, however, revealed that 100% of the ectopic granule cells were from the weaver component of the chimera. Thus, the weaver gene intrinsically affects granule cells in causing ectopia. Other hypothetical sites of gene action would produce a genetically mixed population of ectopic granule cells, which was not the case in this study. These findings are discussed in relation to other abnormalities in the heterozygous weaver mutant and in regard to the Bergmann glia and homozygous mutant. Finally, speculations on the nature of the granule cell deficit are discussed briefly.
实验性小鼠嵌合体被用于确定韦弗突变型小脑基因作用的位点。通过标准胚胎聚集技术产生了包含杂合韦弗（wv/+）和非韦弗（+/+）细胞混合物的嵌合体。选择嵌合体的非韦弗成分，以便在组织学上能够区分浦肯野细胞或颗粒细胞与韦弗浦肯野细胞或颗粒细胞。β-葡萄糖醛酸酶活性水平被用于标记浦肯野细胞，韦弗品系具有高β-葡萄糖醛酸酶活性，而非韦弗品系具有低β-葡萄糖醛酸酶活性。与非鱼鳞病（ic）小鼠相比，鱼鳞病（ic）突变型小鼠中异染色质集中聚集增加被用于标记颗粒细胞群体。在韦弗嵌合体中，与非韦弗对照小鼠相比，小脑尺寸减小，浦肯野细胞和颗粒细胞数量减少，异位浦肯野细胞和颗粒细胞增加。使用葡萄糖醛酸酶细胞标记物发现，异位与基因型之间没有相关性；也就是说，在异位位置发现了基因正常的细胞以及韦弗细胞。因此，在产生杂合韦弗突变体特征性异位方面，韦弗基因在浦肯野细胞外部起作用。然而，对异位颗粒细胞的分析表明，100%的异位颗粒细胞来自嵌合体的韦弗成分。因此，韦弗基因在导致异位方面内在地影响颗粒细胞。基因作用的其他假设位点会产生基因混合的异位颗粒细胞群体，而本研究并非如此。这些发现与杂合韦弗突变体中的其他异常以及伯格曼胶质细胞和纯合突变体相关进行了讨论。最后，简要讨论了对颗粒细胞缺陷性质的推测。
