Cortisone cure of the eyelid closure defect in lidgap-Stein fetal mice: a dose-response and time-response study as a test of the hypomorph hypothesis for the lidgap alleles.
The lidgap-Stein mutation is one of a series of alleles that cause the birth defect open eyes in mice. Previously it was known that cortisone administered during pregnancy prevents the defect in some lidgap-Stein fetuses. In this study, the hypothesis that lidgap-Stein is a hypomorph of effect intermediate between that of its alleles lidgap-Miller (least abnormal) and lidgap-Gates (most abnormal) was tested in a dose-response, time-response, and scanning electron microscopic study. Cortisone produced a response at doses of 20-80 mg/kg, with maximum cure of 30% in right eyes, 24% in left eyes, and 13% bilaterally. There was significantly more response in right than in left eyes. The response was slight at doses of less than 20 mg/kg and dropped to zero at the highest dose of 120 mg/kg. Treatment on days 13 or 14 gave the maximum response, with little or no response to treatment on days 10, 11, 12, 15, or 16. Severity of defect, measured as the size of gap in open eyes on day 18, was not reduced as the frequency of open eyes was reduced; most unclosed eyes remained wide open. The much lower level of maximum bilateral response to cortisone in lidgap-Stein (13%) than in lidgap-Miller (94%) is entirely compatible with the hypomorph hypothesis.
Harris
M J
MJ
Department of Medical Genetics, University of British Columbia, Vancouver, Canada.
D000483:Alleles; D000818:Animals; D003348:Cortisone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005143:Eyelids / Q000002:abnormalities* / Q000187:drug effects / Q000648:ultrastructure; D005260:Female; D005333:Fetus / Q000187:drug effects; D006720:Homozygote; D051379:Mice; D008817:Mice, Mutant Strains; D009154:Mutation; D011247:Pregnancy; D013997:Time Factors
D003348:Cortisone