Huang Dali, Eudy James D, Uzvolgyi Eva, Davis Jack R, Talmadge Catherine B, Pretto Dalyir, Weston Michael D, Lehman Janae E, Zhou Ming, Seemayer Thomas A, Ahmad Iqbal, Kimberling William J, Sumegi Janos
Department of Pathology and Microbiology, Omaha, Nebraska 68198, USA.
Genomics. 2002 Aug;80(2):195-203. doi: 10.1006/geno.2002.6823.
Usher syndrome type IIA (MIM: 27601) is an autosomal recessive disorder characterized by moderate to severe congenital deafness and progressive retinitis pigmentosa. We recently identified the human Usher syndrome type IIA gene (USH2A) on chromosome 1q41, which encodes a protein possessing 10 laminin epidermal growth factor and four fibronectin type 3 domains, both commonly observed in extracellular matrix proteins. To gain insight into the pathogenesis of Usher syndrome type IIA, we isolated and characterized the murine (Ush2a) and rat (rat Ush2a) orthologs of human USH2A. We mapped mouse Ush2a by fluorescence in situ hybridization to mouse chromosome 1 in the region syntenic to human chromosome 1q41. Rat Ush2a has been localized by radiation hybrid mapping to rat chromosome 13 between d13rat49 and d13rat76. The mouse and rat genes, similar to human USH2A, are expressed primarily in retina and cochlea. Mouse Ush2a encodes a 161-kDa protein that shows 68% identity and 9% similarity to the human USH2A protein. Rat Ush2a encodes a 167-kDa protein with 64% identity and 10% similarity to the human protein and 81% identity and 5% similarity to the mouse USH2A protein. The predicted amino acid sequence of the mouse and rat proteins, like their human counterpart, contains a leader sequence, an amino-terminal globular domain, 10 laminin epidermal growth factor domains, and four carboxy-terminal fibronectin type III motifs. With in situ hybridization, we compared the cellular expression of the USH2A gene in rat, mouse, and human retinas. USH2A mRNA in the adult rat, mouse, and human is expressed in the cells of the outer nuclear layer of the retina, one of the target tissues of the disease. In the developing rat retina, Ush2a mRNA expression appears in the neuroepithelium at embryonic day 17.
IIA型Usher综合征（MIM: 27601）是一种常染色体隐性疾病，其特征为中度至重度先天性耳聋和进行性视网膜色素变性。我们最近在1号染色体q41区域鉴定出人类IIA型Usher综合征基因（USH2A），该基因编码一种蛋白质，其具有10个层粘连蛋白表皮生长因子结构域和4个纤连蛋白3型结构域，这两种结构域在细胞外基质蛋白中都很常见。为深入了解IIA型Usher综合征的发病机制，我们分离并鉴定了人类USH2A的小鼠（Ush2a）和大鼠（大鼠Ush2a）直系同源基因。我们通过荧光原位杂交将小鼠Ush2a定位到小鼠1号染色体上与人类1号染色体q41区域同线的区域。大鼠Ush2a已通过辐射杂种图谱定位到大鼠13号染色体上d13rat49和d13rat76之间。与人类USH2A相似，小鼠和大鼠基因主要在视网膜和耳蜗中表达。小鼠Ush2a编码一种161 kDa的蛋白质，与人类USH2A蛋白质具有68%的同一性和9%的相似性。大鼠Ush2a编码一种167 kDa的蛋白质，与人类蛋白质具有64%的同一性和10%的相似性，与小鼠USH2A蛋白质具有81%的同一性和5%的相似性。小鼠和大鼠蛋白质的预测氨基酸序列与其人类对应物一样，包含一个前导序列、一个氨基末端球状结构域、10个层粘连蛋白表皮生长因子结构域和4个羧基末端纤连蛋白III型基序。通过原位杂交，我们比较了USH2A基因在大鼠、小鼠和人类视网膜中的细胞表达情况。成年大鼠、小鼠和人类的USH2A mRNA在视网膜外核层的细胞中表达，视网膜外核层是该疾病的靶组织之一。在发育中的大鼠视网膜中，Ush2a mRNA在胚胎第17天出现在神经上皮中。
