A central nervous system specific mouse model for thanatophoric dysplasia type II.
A central nervous system specific mouse model for thanatophoric dysplasia type II.
复制标题
II 型致死性发育不良的中枢神经系统特异性小鼠模型。
DOI：
10.1093/hmg/ddg309
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发表时间：
2003
影响因子：
3.5
通讯作者：
Francomano,ClairA
中科院分区：
文献类型：
--
作者：
Lin,Ti;Sandusky,StaceyB;Xue,Haipeng;Fishbein,KennethW;Spencer,RichardG;Rao,MahendraS;Francomano,ClairA
为了研究FGFR3 K644E突变对中枢神经系统(CNS)发育的特异性影响，我们将Fgfr3+/K644E-新转基因小鼠与CNS特异性Nestin-cre或软骨特异性Col2a1-cre小鼠杂交，获得了组织特异性TDII小鼠。TDII/Nestin-cre(TDII-N)新生儿没有表现出深刻的骨骼表型。TDII-N幼崽在尾长、前后肢和体重方面与野生型幼崽相当，但许多幼崽表现出明显的圆形头部。MRI和组织化学分析显示TDII-N小鼠皮质厚度和小脑异常的不对称性变化，这与在人类TDII患者中观察到的脑异常相关。这种异常在TDII/Col2a1-cre(TDII-C)小鼠中未见。成体TDII-N脊髓观察发现少突胶质前体细胞提前分化。总体而言，这些数据表明，组织特异性小鼠模型是研究FGFR3在中枢神经系统发育中作用的极佳系统。
To investigate the specific effect of the Fgfr3 K644E mutation on central nervous system (CNS) development, we have generated tissue-specific TDII mice by crossingFgfr3+/K644E-neotransgenic mice with CNS-specific Nestin-cre or cartilage-specific Col2a1-cre mice. TDII/Nestin-cre (TDII-N) neonates did not demonstrate a profound skeletal phenotype.TDII-Npups were comparable to their wild-type littermates in terms of tail length, fore and hindlimbs, and body weight; however, many pups exhibited notably round heads. MRI and histochemical analysis illustrated asymmetric changes in cortical thickness and cerebellar abnormalities inTDII-Nmice, which correlate with brain abnormalities observed in human TDII patients. Such abnormalities were not seen in TDII/Col2a1-cre (TDII-C) mice. Upon examination of adultTDII-Nspinal cord, premature differentiation of oligodendrocyte progenitors was observed. Overall, these data indicate that the tissue-specific mouse model is an excellent system for studying the role of Fgfr3 in the developing CNS.