Middle ear defects associated with the double knock out mutation of murinegoosecoid and Msx1 genes

A number of developmental regulatory genes, including homeobox genes, are d ynamically expressed in the mammalian cephalic ectomesenchyme during cranio facial morphogenesis, Owing to the vast amount of gene knock out experiment s, functions of such genes are now being revealed in the mammalian skeletal patterning process. The murine goosecoid (Gsc) and Msxl genes are expresse d during craniofacial development and each mutant mouse displays intriguing facial abnormalities including those of middle ear ossicles, suggesting th at both genes play roles in spatial programming of craniofacial regions. In order to examine whether these genes could function in concert to direct p articular craniofacial morphogenesis, double knock out mice were analyzed. The phenotype of the double mutant mice was restricted to the first arch de rivatives and was apparently additive of the single gene mutant mice, imply ing region specific genetic interactions of these homeobox genes expressed in overlapping regions of middle ear forming ectomesenchyme. Our results al so suggested that the patterning of distal portions of the malleus depends on the tympanic membrane, for which normal expressions of both the genes ar e prerequisite.