Generation of Fgfr3 conditional knockout mice.
Generation of Fgfr3 conditional knockout mice.
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Fgfr3 条件性基因敲除小鼠的产生
DOI：
10.7150/ijbs.6.327
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发表时间：
2010-06-15
影响因子：
9.2
通讯作者：
Chen L
中科院分区：
文献类型：
--
作者：
Su N;Xu X;Li C;He Q;Zhao L;Li C;Chen S;Luo F;Yi L;Du X;Huang H;Deng C;Chen L
成纤维细胞生长因子受体3(FGFR3)在人和小鼠体内高度保守，是成纤维细胞生长因子的关键酪氨酸激酶受体之一。FGFR3在不同发育阶段的软骨、脑、肾、肠等组织中均有表达。传统的FGFR3等位基因敲除导致寿命短，骨骼过度生长。在临床上，人类FGFR3基因突变导致三种不同类型的软骨发育不良综合征，包括软骨发育不良(ACH)、软骨发育不良(HCH)和死亡性发育不良(TD)。为了更好地了解FGFR3在不同发育阶段不同组织中的作用以及在病理条件下的作用，我们建立了FGFR3条件性基因敲除小鼠，其中loxP位点位于FGFR3等位基因第9-10外显子的两侧。我们还证明了Cre介导的重组使用Col2a1-Cre，一个在骨发育过程中在软骨细胞中表达的Cre系，导致含有软骨的组织中该基因的特异性缺失。该动物模型将有助于研究FGFR3在不同年龄不同组织中的不同作用。
Fibroblast growth factor receptor 3 (FGFR3), highly conserved in both humans and murine, is one of key tyrosine kinase receptors for FGF. FGFR3 is expressed in different tissues, including cartilage, brain, kidney, and intestine at different development stages. Conventional knockout of Fgfr3 alleles leads to short life span, and overgrowth of bone. In clinic, human FGFR3 mutations are responsible for three different types of chondrodysplasia syndromes including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD). For better understanding of the roles of FGFR3 in different tissues at different stages of development and in pathological conditions, we generated Fgfr3 conditional knockout mice in which loxp sites flank exons 9-10 in the Fgfr3 allele. We also demonstrated that Cre-mediated recombination using Col2a1-Cre, a Cre line expressed in chondrocyte during bone development, results in specific deletion of the gene in tissues containing cartilage. This animal model will be useful to study distinct roles of FGFR3 in different tissues at different ages.