Toward positional cloning of the curly tail gene.

作者信息

Brouns Madeleine R, Peeters Marian C E, Geurts Jan M, Merckx Diane M, Engelen John J, Hekking Johan W M, Terwindt-Rouwenhorst Els A W, Oosterbaan Mariet E A C, Geraedts Joep P M, van Straaten Henny W

机构信息

Department of Anatomy and Embryology, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands.

出版信息

Birth Defects Res A Clin Mol Teratol. 2005 Mar;73(3):154-61. doi: 10.1002/bdra.20109.

DOI:10.1002/bdra.20109

PMID:15678492

Abstract

BACKGROUND

The curly tail (ct) mutant mouse is one of the best-studied mouse models of spina bifida. The ct mutation has been localized to distal chromosome 4 in two independent studies and was recently postulated to be in the Grhl-3 gene.

METHODS

A recombinant BALB/c-ct strain was generated and used to precisely map the ct gene.

RESULTS

We report the absence of gross chromosomal abnormalities and the precise mapping of the ct gene to a 3-Mb region at 135 Mb (66 cM) from the centromere, closely linked to the polymorphic microsatellite marker D4Mit148. Candidate genes, Idb3, Wnt4, Cdc42, and perlecan, all localized in the critical region, were studied by sequence and expression analyses. Our data indicate that these genes in all probability do not account for the ct phenotype. In addition, our expression data do not provide strong evidence that Grhl-3 is indeed the ct gene.

CONCLUSIONS

The ct gene has not yet been identified. A total of 29 candidate genes remain present in the critical region. Refined mapping studies need to be performed to further narrow the region and additional candidate genes need to be examined. Supplementary material for this article can be found on the Birth Defects Research (Part A) website (http://www.mrw.interscience.wiley.com/suppmat/1542-0752/suppmat/2005/73/tables_S3-S6.doc).

摘要