MORPHOMETRIC ANALYSIS OF HETEROZYGOTE DANCER MICE PREDISPOSED TO 6-AMINONICOTINAMIDE-INDUCED CLEFT-LIP

Mid-facial development is an extremely complex process involving coord inated events and precise timing. Cleft lip (CL) may result from the f ailed fusion of the lateral and medial nasal processes in the developi ng embryo. It has been postulated that spontaneous CL in the A/J strai n of mice may be due to a predisposing face shape (Trasler, '68). This hypothesis was examined in mutant mice susceptible to teratogen-induc ed CL. Mice carrying the dancer (Dc) mutation in the heterozygous stat e rarely develop CL, whereas 90% of homozygotes (Dc/Dc) develop CL. Ou tcrossed heterozygotes show elevated susceptibility to 6-aminonicotina mide (6AN)-induced CL (Trasler et al., '84) and these were used to inv estigate face shape as a predisposing factor. Dc/ + and +/+ males were mated to R stock females, and embryos were collected on day 10/21 hr, when the nasal placodes are approximately at the oblong or crescent s tage. Total nasal process areas and volumes, medial and lateral proces s areas and volumes, and medial jut lengths were measured from histolo gical sections, and comparisons made between the two populations. The results indicate that compared to +/+ control, heads of embryos from t he Dc/ + cross have significantly smaller mean total process areas and volumes (P < 0.005), mean lateral process areas and volumes (P < 0.00 5), mean medial process area and volumes (P < 0.01), mean maximum head diameter (P < 0.02), but similarly sized medial juts and crown rump l engths. Correlations between maximum head diameter and process size in dicate that the Dc mutation may hinder normal development of the nasal processes. These reduced nasal processes may explain the underlying p redisposition to 6AN-induced CL.