MOUSE PALATAL WIDTH GROWTH-RATES AS AN AT RISK FACTOR IN THE DEVELOPMENT OF CLEFT-PALATE INDUCED BY HYPERVITAMINOSIS-A

Epidemiological studies revealed population differences in the frequen cy of cleft lip and palate, with wide faced, rapid growing populations having the highest incidence: Mongoloids>Caucasoids> Blacks. Laborato ry studies have also demonstrated higher incidence of vitamin A-induce d cleft palate in both rats and mice with rapid somatic growth rates c ompared to those with slower rates. The present study was designed to test the hypothesis that palatal width growth rates are significantly correlated with frequencies of cleft palate induced by hypervitaminosi s A in seven strains of mice. Palatal width growth rates were calculat ed using 158 fetuses from 26 timed pregnant mice. Anterior and posteri or palatal width growth rates during secondary palatogenesis were calc ulated between day 15 (n=88) and day 18 (n=70) gestational age. Anteri or palatal width rates ranged from 0.106 mm/day (BALB/cByJ) to 0.219 m m/day (C57BL/6J), and rates for the posterior measure ranged from 0.11 1 mm/day (BALB/cByJ) to 0.179 mm/day (CBA/J). Vitamin A (10,000 IU/kg) was administered to an additional 26 timed pregnant mice on day 10 of gestation. The frequency of clefting, calculated from 181 fetuses at day 18 of gestation, was found to range from 52.4% +/- 9.7 (C3H/HeJ) t o 96.3 +/- 6.4 (CBA/J). No significant correlation (P>0.05) was found between palatal width growth rates and the frequencies of vitamin A in duced cleft palate. It is concluded that if the rate of growth in the width of the palate is causative in clefting, it must be a pre-cleftin g (i.e., pre-shelf elevation) event and may only be detectable earlier than day 15 of gestation in the mouse.