6-Aminonicotinamide-induced cleft palate in the mouse: The nature of the difference between the A/J and C57BL/6J strains in frequency of response and its genetic basis

Abstract

Cleft palate induction by 6-aminonicotinamide (6-AN) was examined in the A/J and C57BL/6J strains of mice to determine the nature of the strain difference in frequency of cleft-palate response. Probit analysis of the cleft-palate response to dose of different genotypes revealed a family of linear and parallel dose-response curves. The genotypes differ only in dosage tolerance (log ED₅₀) to 6-AN that is required for the cleft-palate response. No evidence for a maternal cytoplasmic effect on 6-AN-induced cleft palate was found under the conditions of the present study. When the difference in dosage tolerance to 6-AN between A/J and C57BL/6J was examined with a single dose and measured by differences in frequency of induced cleft palate on a probit scale, there was some departure from genetic additivity. There was an indication of dominance deviation of the F₁ embryos in the direction of C57BL/6J. A 3-locus, epistatic model is proposed to account for the difference in embryonic tolerance to 6-AN-induced cleft palate. There was a suggestion of association with the brown (b) locus.