THE VARIABLE EXPRESSIVITY AND INCOMPLETE PENETRANCE OF THE TWIST-NULLHETEROZYGOUS MOUSE PHENOTYPE RESEMBLE THOSE OF HUMAN SAETHRE-CHOTZEN-SYNDROME

Most targeted gene mutations are recessive and analyses of gene functi on often focus on homozygous mutant phenotypes, Here we describe parts of the expression pattern of M-twist in the head of developing wild-t ype mice and present our analysis of the phenotype of heterozygous twi st-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 f ormation and the role of M-twist during this process, as within the sa me 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 i dentified in patients affected with Saethre-Chotzen syndrome (SCS). Ex pressivity of this syndrome is variable, although most patients presen t 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 etio logy of morphological abnormalities that appear in human patients affe cted by other syndromes.