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Sox18 mutations in the ragged mouse alleles ragged‐like and opossum

2003; Wiley; Volume: 36; Issue: 1 Linguagem: Inglês

10.1002/gene.10190

1526-968X

Kristy M. James, Brett Hosking, Jennifer M. Gardner, George E.O. Muscat, Peter Koopman,

Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

Abstract Summary: The ragged ( Ra ) spontaneous mouse mutant is characterised by abnormalities in its coat and cardiovascular system. Four alleles are known and we have previously described mutations in the transcription factor gene Sox18 in the Ra and Ra J alleles. We report here Sox18 mutations in the remaining two ragged alleles, opossum ( Ra op ) and ragged‐like ( Ragl ). The single‐base deletions cause a C‐terminal frameshift, abolishing transcriptional trans ‐activation and impairing interaction with the partner protein MEF2C. The nature of these mutations, together with the near‐normal phenotype of Sox18 ‐null mice, suggests that the ragged mutant SOX18 proteins act in a dominant‐negative fashion. The four ragged mutants represent an allelic series that reveal SOX18 structure–function relationships and implicate related SOX proteins in cardiovascular and hair follicle development. genesis 36:1–6, 2003. © 2003 Wiley‐Liss, Inc.