PENETRANCE AND EXPRESSIVITY OF ACETAZOLAMIDE-ECTRODACTYLY PROVIDE A METHOD TO DEFINE A RIGHT-LEFT TERATOGENIC GRADIENT THAT DIFFERS BETWEENTHE C57BL 6J AND WB/REJ MOUSE STRAINS/

Penetrance or the frequency of embryos with any degree of forelimb ect rodactyly is the usual method to describe the forelimb ectrodactyly re sponse of mouse embryos to acetazolamide. A digit score for number of small or absent digits for the separate right and left forelimb respon se to acetazolamide provides a measure of expressivity or the severity of response. We examine the relationship between expressivity and pen etrance using right and left forelimb data from a previously reported dose-response analysis of the C57BL/6J and WB/ReJ strains to acetazola mide. The data show that expressivity and penetrance are highly correl ated for the separate right and left forelimbs for both strains. In C5 7BL/6J, the dose-response analyses of both expressivity and penetrance of the separate right and left forelimbs demonstrate a teratogenic gr adient, decreasing from right to left, that depends on the symmetrical ectrodactyly response of the right and left forelimbs. In WB/ReJ, the right forelimb is also more sensitive than the left, but the dose-res ponse analyses of both penetrance and expressivity show the two foreli mbs are asymmetrical in their ectrodactyly response and that there is not a simple teratogenic gradient in this strain. In WB/ReJ, the left forelimb is resistant at even the highest non-lethal doses. The high c orrelation between expressivity and penetrance for the separate foreli mbs of both C57BL/6J and WB/ReJ suggests that this right-left differen ce between the two strains may not be a property of the limbs themselv es but may be an intrinsic genetic difference between the two types of embryos perhaps in the amount of teratogen to which the embryos are e xposed. The right and left forelimbs of the embryo may simply provide a biological assay of this intrinsic embryonic difference.