Genetic mapping of an insertional hydrocephalus-inducing mutation allelic to hy3.
Genetic mapping of an insertional hydrocephalus-inducing mutation allelic to hy3.
复制标题
hy3 插入性脑积水诱导突变等位基因的遗传图谱。
DOI：
10.1007/s00335-002-2201-8
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Harrison,WilburR
中科院分区：
文献类型：
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作者：
Robinson,MichaelL;Allen,CarlE;Davy,BrianE;Durfee,WilliamJ;Elder,FrederickF;Elliott,ChristopherS;Harrison,WilburR
转基因小鼠系OVE459携带转基因诱导的插入突变，导致常染色体隐性先天性脑积水。纯合子转基因动物在围产期开始心室扩张，并且在出生后几天内明显小于半合子或非转基因的窝友。荧光原位杂交（FISH）显示，该转基因基因插入小鼠染色体8 (chr) D2-E1区单个位点。半合子OVE459小鼠与自发突变脑积水-3 （hy3）的杂合小鼠的遗传杂交产生脑积水后代的频率为22%，表明这两种突变是等位基因。利用纯合子OVE459小鼠的DNA建立基因组文库，分离转基因插入位点两侧的基因组DNA并测序。利用Jackson实验室Backcross DNA Panel Mapping Resource，利用C57BL/6 DNA与Mus spretus之间的PCR多态性，将转基因插入片段定位在D8Mit152近1.06 cM±0.75处。此外，对转基因插入位点两侧独特标记阳性的小鼠细菌人工染色体（BAC）克隆的序列分析表明，转基因插入位点两侧的基因组dna在野生型小鼠染色体上物理分离约51 kb。
The transgenic mouse line OVE459 carries a transgene-induced insertional mutation resulting in autosomal recessive congenital hydrocephalus. Homozygous transgenic animals experience ventricular dilation with perinatal onset and are noticeably smaller than hemizygous or non-transgenic littermates within a few days after birth. Fluorescence in situ hybridization (FISH) revealed that the transgene inserted in a single locus on mouse Chromosome (chr) 8, region D2-E1. Genetic crosses between hemizygous OVE459 mice and mice heterozygous for the spontaneous mutation hydrocephalus-3 (hy3) produced hydrocephalic offspring with a frequency of 22%, demonstrating that these two mutations are allelic. A genomic library was made by using DNA from homozygous OVE459 mice, and genomic DNA flanking the transgene insertion site was isolated and sequenced. A PCR polymorphism between C57BL/6 DNA and Mus spretus was used to map the location of the transgene insert to 1.06 cM ± 0.75 proximal to D8Mit152 by using the Jackson Laboratory Backcross DNA Panel Mapping Resource. Furthermore, sequence analysis from a mouse bacterial artificial chromosome (BAC) clone, positive for unique markers on both sides of the transgene insertion site, demonstrated that the genomic DNAs flanking each side of the transgene insertion are physically separated by approximately 51 kb on the wild-type mouse chromosome.