Inversin, a novel gene in the vertebrate left-right axis pathway, is partially deleted in the inv mouse

被引:193
作者
Morgan, D
Turnpenny, L
Goodship, J [1 ]
Dai, WL
Majumder, K
Matthews, L
Gardner, A
Schuster, G
Vien, L
Harrison, W
Elder, FEB
Penman-Splitt, M
Overbeek, P
Strachan, T
机构
[1] Newcastle Univ, Dept Human Genet, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England
[2] Baylor Coll Med, Dept Cell Biol, Houston, TX 77030 USA
[3] Baylor Coll Med, Dept Mol & Human Genet, Houston, TX 77030 USA
[4] Sanger Ctr, Cambridge CB10 1RQ, England
[5] Univ Texas, Hlth Sci Ctr, Dept Pathol & Lab Med, Houston, TX 77030 USA
基金
英国惠康基金;
关键词
D O I
10.1038/2450
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Visceral left-right asymmetry occurs in all vertebrates, but the inversion of embryo turning (inv) mouse, which resulted following a random transgene insertion, is the only model in which these asymmetries are consistently reversed(1). We report positional cloning of the gene underlying this recessive phenotype. Although transgene insertion was accompanied by neighbouring deletion and duplication events(1,2), our YAC phenotype rescue studies indicate that the mutant phenotype results from the deletion. After extensively characterizing the 47-kb deleted region and flanking sequences from the wild-type mouse genome, we found evidence for only one gene sequence in the deleted region. We determined the full-length 5.5-kb cDNA sequence and identified 16 exons, of which exons 3-11 were eliminated by the deletion, causing a frameshift. The novel gene specifies a 1062-aa product with tandem ankyrin-like repeat sequences. Characterization of complementing and non-complementing YAC transgenic families revealed that correction of the inv mutant phenotype was concordant with integration and intact expression of this novel gene, which we have named inversin (Invs).
引用
收藏
页码:149 / 156
页数:8
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