Penetrance and expressivity of acetazolamide-ectrodactyly provide a method to define a right-left teratogenic gradient that differs between the C57BL/6J and WB/ReJ mouse strains.
Penetrance or the frequency of embryos with any degree of forelimb ectrodactyly is the usual method to describe the forelimb ectrodactyly response of mouse embryos to acetazolamide. A digit score for number of small or absent digits for the separate right and left forelimb response to acetazolamide provides a measure of expressivity or the severity of response. We examine the relationship between expressivity and penetrance using right and left forelimb data from a previously reported dose-response analysis of the C57BL/6J and WB/ReJ strains to acetazolamide. The data show that expressivity and penetrance are highly correlated for the separate right and left forelimbs for both strains. In C57BL/6J, the dose-response analyses of both expressivity and penetrance of the separate right and left forelimbs demonstrate a teratogenic gradient, 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-response analyses of both penetrance and expressivity show the two forelimbs 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 correlation between expressivity and penetrance for the separate forelimbs of both C57BL/6J and WB/ReJ suggests that this right-left difference between the two strains may not be a property of the limbs themselves but may be an intrinsic genetic difference between the two types of embryos perhaps in the amount of teratogen to which the embryos are exposed.(ABSTRACT TRUNCATED AT 250 WORDS)
Biddle
F G
FG
Department of Pediatrics, University of Calgary, Alberta, Canada.
Mulholland
L R
LR
Eales
B A
BA
D000014:Abnormalities, Drug-Induced / Q000196:embryology*; D000086:Acetazolamide / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D005552:Forelimb / Q000002:abnormalities*; D051379:Mice; D008810:Mice, Inbred C57BL; D011247:Pregnancy; D013045:Species Specificity
D000086:Acetazolamide