Gly374Arg mutation in Fgfr3 causes achondroplasia in mice / 中华医学遗传学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To establish the mouse model of Gly374Arg mutation in fibroblast growth factor receptor 3(Fgfr3) and to analyze the phenotype of the mutant mice.</p><p><b>METHODS</b>The double PCR was used to introduce Gly374Arg point mutation into mouse Fgfr3. The electroporation of embryonic stem(ES) cells was carried out with targeting vector. The targeted ES cells were screened by Positive-Negative Selection of G418 and Ganciclovir, and Southern blot. The correct targeted ES cells were microinjected into blastula. Finally, mutant mice were obtained by crossing between EIIa-Cre transgenic mice and mice carrying recombined mutant Fgfr3 allele. The mice were genotyped by PCR, and phenotype was observed by skeleton staining, histology, etc.</p><p><b>RESULTS</b>Fgfr3-Gly374Arg mutant mice exhibited small size, short tail, macrocephaly and had dome-shaped heads, the epiphyseal growth plates of mutant mice were narrower, and the hypertrophic chondrocyte zone was also obviously decreased. Meanwhile, the majority of female mice were infertile, and the uterus, ovary and mammal gland in mutant female mice were also smaller and underdeveloped.</p><p><b>CONCLUSION</b>The model of Fgfr3-Gly374Arg mutation causing achondroplasia in mice has been established successfully.</p>