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 functionoften focus on homozygous mutant phenotypes. Here we describe parts of theexpression pattern of M-twist in the head of developing wild-type mice andpresent our analysis of the phenotype of heterozygous twist- null animalsat around birth and in adults. A number of twist -null heterozygous micepresent skull and limb defects and, in addition, we observed othermalformations, such as defects in middle ear formation and the xyphoidprocess. Our study is of interest to understand bone formation and the roleof M-twist during this process, as within the same animal growth of somebones can be accelerated while for others it can be delayed. Moreover, weshow here that expressivity of the mouse mutant heterozygous phenotype isdependent on the genetic background. This information might also be helpfulfor clinicians, since molecular defects affecting one allele of the humanH-twist ( TWIST ) gene were identified in patients affected withSaethre-Chotzen syndrome (SCS). Expressivity of this syndrome is variable,although most patients present craniofacial and limb malformationsresembling those seen in mutant mice. Thus the mutant mouse twist -nullstrain might be a useful animal model for SCS. The twist -null mutant mousemodel, combined with other mutant mouse strains, might also help in anunderstanding of the etiology of morphological abnormalities that appear inhuman patients affected by other syndromes.