The hairless gene of the mouse: Relationship of phenotypic effects with expression profile and genotype

Various mutations of the hairless (hr) gene of mice result in hair loss and other integument defects. To examine the role of the hr gene in mouse deve lopment, the expression profile of hr has been determined by in situ hybrid isation and correlated to the nature of genetic changes and morphological a bnormalities in different mutant animals. Four variant alleles have been ch aracterised at the molecular level. hr/hr mice produce reduced, but signifi cant, levels of hr mRNA whereas other alleles contain mutations which would be expected to preclude the synthesis of functional product, demonstrating a correlation between allelic variation at the hr locus and phenotypic sev erity. hr expression was shown to be widespread and temporally regulated. I t was identified in novel tissues such as cartilage, developing tooth, inne r ear, retina, and colon as well as in skin and brain. Analysis of mice hom ozygous for the rhino allele of hairless revealed that, although no morphol ogical defects were detectable in many tissues normally expressing hr, prev iously undescribed abnormalities were present in several tissues including inner ear, retina, and colon, These findings indicate that the hairless gen e product plays a wider role in development than previously suspected. Dev Dyn 1999;216:113-126, (C) 1999 Wiley-Liss, Inc.