| Research Abstract |
To get an insight into the genetical predisposition and pathogenesis of the hemifacial microsomia (HFM), we analyzed the mutant locus of the HFM model mouse. By the P1 phage library screening, we isolated the chromosomal DNA from the mutant region. By the DNA sequencing, we screened the coding regions that corresponded to the mutant gene(s). At present, we sequenced about 10 kb, then we identified some regions that had highly homologous sequences with those of some known genes. These genes locate the different loci with HFM locus, then it is suggested that the gene(s) that responds to HFM pathogenesis is a nobel gene, and shares some domain structures to the known genes.
We investigated the phenotype of homo-zygote of HFM mouse. By the natural mating between the hemi zygotes, we obtained 12 embryos at E9.5. Three embryos died as the rosy mass. PCR analysis showed that one of three embryos was a homo-zygote (another two embryos could not determine their genotypes due to DNA degradation). According to the size of the placenta, homo-zygotes embryo developed normally to E7.5. These results showed that the gene that disrupted in HFM mouse had an essential role for the normal development.
The pathological screening was carried out at the late prenatal days (E13.5-17.5). In addition to the branchial arch anomalies that described previously, other anomalies and asymmetries at the maxilla, mandible, zygoma and facial soft tissue ware identified. These observation further supported that HFM mouse is a suitable animal model for the human HFM at the point of the pathological characteristics.
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