Triarhou L C, Solà C, Palacios J M, Mengod G
Department of Pathology and Laboratory Medicine, Indiana University School of Medicine, Indianapolis 46202-5120, USA.
Arch Histol Cytol. 1998 Aug;61(3):233-42. doi: 10.1679/aohc.61.233.
MAP2 is a major microtubule-associated brain protein, selectively localized in dendrites; growth-associated phosphoprotein GAP-43 is a neuron-specific protein associated with axonal outgrowth. In adult cerebellum, both of these proteins and their corresponding RNA transcripts are most strongly expressed by granule cells. Using immunocytochemistry with antibodies and in situ hybridization histochemistry with [32P] labeled oligonucleotide probes, we examined the cellular localization of MAP2, GAP-43 and their mRNAs in the cerebellum of control and weaver (wv/wv) mutant mice, which exhibit massive granule cell death. In wild-type (+/+) mice, MAP2 immunoreactivity was seen in neuronal somata and dendrites of the granule cell layer; GAP-43 immunoreactivity was present in molecular layer, corresponding to the distribution of parallel fibres. Transcripts encoding MAP2 and GAP-43 were localized in the layer of the granule cell somata. In heterozygous weaver mice (wv/+), which feature an intermediate degree of granule cell loss, MAP2 immunoreactivity was localized in the granular layer, and the pattern of GAP-43 immunostaining was also similar to +/+, the only difference being a thinner molecular layer. Heterozygotes had an anatomical pattern of MAP2 and GAP-43 mRNA hybridization qualitatively similar to that of the wild-type with some deviations in signal intensity. In homozygous weaver mutants (wv/wv), MAP2 immunoreactivity was extremely weak in the area beneath Purkinje cells and a certain GAP-43 immunoreactivity was seen in the upper part of cerebellar cortex. Hybridization signals for MAP2 and GAP-43 mRNAs were minimal. The reported alterations in regional pattern of MAP2 and GAP-43 expression in mutant mice offer a molecular correlate of dendritic and axonal protein gene transcription pertinent to the neuropathological manifestations of certain forms of heredodegenerative ataxia.
微管相关蛋白2（MAP2）是一种主要的与微管相关的脑蛋白，选择性地定位于树突中；生长相关磷酸蛋白GAP - 43是一种与轴突生长相关的神经元特异性蛋白。在成年小脑中，这两种蛋白及其相应的RNA转录本在颗粒细胞中表达最为强烈。我们使用抗体免疫细胞化学和[32P]标记的寡核苷酸探针原位杂交组织化学方法，研究了对照小鼠和表现出大量颗粒细胞死亡的韦弗（wv/wv）突变小鼠小脑中MAP2、GAP - 43及其mRNA的细胞定位。在野生型（+/+）小鼠中，MAP2免疫反应性见于颗粒细胞层的神经元胞体和树突；GAP - 43免疫反应性存在于分子层，与平行纤维的分布相对应。编码MAP2和GAP - 43的转录本定位于颗粒细胞胞体层。在具有中等程度颗粒细胞丢失特征的杂合子韦弗小鼠（wv/+）中，MAP2免疫反应性定位于颗粒层，GAP - 43免疫染色模式也与+/+相似，唯一的区别是分子层较薄。杂合子MAP2和GAP - 43 mRNA杂交的解剖模式在质量上与野生型相似，只是信号强度存在一些偏差。在纯合子韦弗突变体（wv/wv）中，MAP2免疫反应性在浦肯野细胞下方区域极其微弱，在小脑皮质上部可见一定的GAP - 43免疫反应性。MAP2和GAP - 43 mRNA的杂交信号极少。报道的突变小鼠中MAP2和GAP - 43表达区域模式的改变为与某些形式的遗传性共济失调神经病理表现相关的树突和轴突蛋白基因转录提供了分子关联。
