Abstract
Cleft lip and/or cleft palate (CLP) is one of the most common malformations in new born infants and seem to be caused by a combination of genetic and environmental factors. A particular mouse strain, CL/Fr mice, shows a high incidence of CLP, suggesting involvement of genetic factors, though genes relevant are not identified. p53 tumour suppressor gene could affect CLP development because p53 prevents malformations such as exencephaly probably by inducing apoptosis of damaged cells that result in developmental abnormalities. On the other hand, there are reports that γ-irradiation, an environmental factor, increases the incidence of CLP in their offspring. p53 is a well-known sensor and signaling protein of radiation-induced damages, however effect of p53 on radiation-induced CLP is not investigated. Thus, we produced the p53-deficient CL/Fr and examined CLP in mouse embryos. p53-deficient allele of p53(KO/+)BALB/c was introduced into CL/Fr by a speed congenic method. p53(KO/+)CL/Fr generated are then mated each other and pregnant females were sacrificed on 18.5 day of gestation. Embryos were p53-genotyoped and the incidence of spontaneous CLP was examined. The incidence was 20% in p53(+/+) and p53(KO/+) and 13% in p53(KO/KO), indicating no significant difference between the two different classes of p53 genotype. This suggests that p53 does not impact the incidence of spontaneous CLP. Then, to know effect of radiation, we are examining embryos that were exposed to γ-irradiation on 9.5 day of gestation. Results of incidence and radiation effect will be reported.
