Cloning and characterization of the murine Vmd2 RFP-TM gene family
Cloning and characterization of the murine Vmd2 RFP-TM gene family
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DOI：
10.1159/000078016
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发表时间：
2004-01-01
影响因子：
1.7
通讯作者：
Weber, BHF
中科院分区：
文献类型：
--
作者：
Krämer, F;Stöhr, H;Weber, BHF
已知人卵黄状黄斑营养不良2型（VMD 2）基因中的突变引起常染色体显性Best黄斑营养不良（BMD），一种中央视网膜的退行性疾病。VMD 2与VMD 2L 1、VMD 2L 2和VMD 2L 3一起属于密切相关的基因家族，其特征在于多个跨膜（TM）螺旋结构域和不变的精氨酸、苯丙氨酸和脯氨酸（RFP）三肽基序，因此称为VMD 2 RFP-TM。这四个基因被认为编码一个新的阴离子通道家族。我们现在报告的克隆和表征的小鼠直系同源物相结合的生物计算分析和分子遗传学方法。虽然鼠Vmd 2、Vmd 2l 1和Vmd 2l 3基因是功能性的，但发现鼠Vmd 2l 2 p是非转录的假基因。鼠Vmd 2 RFP-TM家族成员的表达谱显示组织限制性表达，其中睾丸中Vmd 2、结肠中Vmd 2l 1和心脏中Vmd 2l 3的主要转录。Vmd 2l 3在许多组织中（例如在脑、视网膜/RPE、肾中）观察到差异剪接，尽管剪接变体的功能重要性仍有待确定。版权所有（C）2003 S. Karger AG，巴塞尔。
Mutations in the human vitelliform macular dystrophy type 2 (VMD2) gene are known to cause autosomal dominant Best macular dystrophy (BMD), a degenerative disorder of the central retina. VMD2, together with VMD2L1, VMD2L2 and VMD2L3, belong to a closely related gene family characterized by several transmembrane (TM) spanning helical domains and an invariant arginine, phenylalanine and proline (RFP) tripeptide motif, thus termed VMD2 RFP-TM. The four genes are thought to encode a novel family of anion channels. We now report the cloning and characterization of the murine orthologs by combining biocomputational analyses and molecular genetic approaches. While the murine Vmd2, Vmd2l1 and Vmd2l3 genes are functional, murine Vmd2l2p was found to be a non-transcribed pseudogene. Expression profiling of the murine Vmd2 RFP-TM family members revealed tissue-restricted expression with predominant transcription of Vmd2 in testis, of Vmd2l1 in colon and of Vmd2l3 in heart. Differential splicing was observed for Vmd2l3 in a number of tissues (e.g. in brain, retina/RPE, kidney) although the functional importance of the splice variants remains to be determined. Copyright (C) 2003 S. Karger AG, Basel.