Characterization of the Crumbs homolog 2 (CRB2) gene and analysis of its role in retinitis pigmentosa and Leber congenital amaurosis.-猫眼课题宝

DOI：

发表时间：

2005-04

期刊：

Molecular vision

影响因子：

2.2

通讯作者：

中科院分区：

医学4区

文献类型：

作者：

J. A. van den Hurk;P. Rashbass;R. Roepman;Jason A Davis;K. Voesenek;M. Arends;Marijke N. Zonneveld;M. van Roekel;K. Cameron;K. Rohrschneider;J. Heckenlively;R. Koenekoop;C. Hoyng;F. Cremers;A. D. den Hollander

目的CRB 1基因突变引起常染色体隐性视网膜色素变性（RP）和Leber先天性黑蒙（LCA）。数据库搜索揭示了染色体9q33.3和19p13.3上的另外两个Crumbs同源物。本研究的目的是描述9q33.3上的Crumbs同源物2（CRB 2）基因，分析其表达模式，并确定CRB 2中的突变是否与RP和LCA相关。方法采用逆转录-聚合酶链反应（RT-PCR）技术检测CRB 2 mRNA及其在人体组织中的表达。采用mRNA原位杂交技术检测Crb 2在小鼠眼组织中的表达。通过单链构象分析和直接核苷酸测序对85例RP患者和79例LCA患者的CRB 2开放阅读框和剪接点进行突变分析。结果CRB 2基因由13个外显子组成，编码一个1285个氨基酸的跨膜蛋白。CRB 2主要在视网膜、脑和肾脏中表达。在小鼠视网膜中，在所有细胞层中检测到Crb 2表达。CRB 2基因的突变分析揭示了11个导致氨基酸取代的序列变体。其中三个在对照个体中未被识别，并影响保守的氨基酸残基。然而，携带这些序列变异的患者在另一个等位基因上没有第二个序列变异，排除了CRB 2序列变异的常染色体隐性遗传作为其疾病的原因。结论CRB 2序列变异不是常染色体隐性遗传RP和LCA的常见病因。由于CRB 2在视网膜以外的组织中表达，更复杂的临床表型可能与CRB 2在人类中的功能丧失或改变相关。

PURPOSE Mutations in the Crumbs homolog 1 (CRB1) gene cause autosomal recessive retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA). Database searches reveal two other Crumbs homologs on chromosomes 9q33.3 and 19p13.3. The purpose of this study was to characterize the Crumbs homolog 2 (CRB2) gene on 9q33.3, to analyze its expression pattern, and to determine whether mutations in CRB2 are associated with RP and LCA. METHODS The CRB2 mRNA and its expression pattern in human tissues were analyzed by reverse transcription-polymerase chain reaction (RT-PCR). The cellular expression of Crb2 in the mouse eye was determined by mRNA in situ hybridizations. The open reading frame and splice junctions of CRB2 were analyzed for mutations by single-strand conformation analysis and direct nucleotide sequencing in 85 RP patients and 79 LCA patients. RESULTS The CRB2 gene consists of 13 exons and encodes a 1285 amino acid transmembrane protein. CRB2 is mainly expressed in retina, brain, and kidney. In mouse retina Crb2 expression was detected in all cell layers. Mutation analysis of the CRB2 gene revealed 11 sequence variants leading to an amino acid substitution. Three of them were not identified in control individuals and affect conserved amino acid residues. However, the patients that carry these sequence variants do not have a second sequence variant on the other allele, excluding autosomal recessive inheritance of CRB2 sequence variants as a cause of their disease. CONCLUSIONS This study shows that CRB2 sequence variants are not a common cause of autosomal recessive RP and LCA. It is possible that a more complex clinical phenotype is associated with the loss or altered function of CRB2 in humans due to its expression in tissues other than the retina.

Characterization of the Crumbs homolog 2 (CRB2) gene and analysis of its role in retinitis pigmentosa and Leber congenital amaurosis.

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