The Variable Expressivity and Incomplete Penetrance of the twist-Null Heterozygous Mouse Phenotype Resemble Those of Human Saethre-Chotzen Syndrome

Most targeted gene mutations are recessive and analyses of gene function often focus on homozygous mutant phenotypes. Here we describe parts of the expression pattern of M-twist in the head of developing wild-type mice and present our analysis of the phenotype of heterozygous twist-null animals at around birth and in adults. A number of twist-null heterozygous mice present skull and limb defects and, in addition, we observed other malformations, such as defects in middle ear formation and the xyphoid process. Our study is of interest to understand bone formation and the role of M-twistduring this process, as within the same animal growth of some bones can be accelerated while for others it can be delayed. Moreover, we show here that expressivity of the mouse mutant heterozygous phenotype is dependent on the genetic background. This information might also be helpful for clinicians, since molecular defects affecting one allele of the human H-twist (TWIST) gene were identified in patients affected with Saethre-Chotzen syndrome (SCS). Expressivity of this syndrome is variable, although most patients present craniofacial and limb malformations resembling those seen in mutant mice. Thus the mutant mouse twist-null strain might be a useful animal model for SCS. The twist-null mutant mouse model, combined with other mutant mouse strains, might also help in an understanding of the etiology of morphological abnormalities that appear in human patients affected by other syndromes.