Generation of a conditional disruption of the Tsc2 gene
Generation of a conditional disruption of the Tsc2 gene
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DOI：
10.1002/dvg.20271
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发表时间：
2007-02-01
期刊：
影响因子：
1.5
通讯作者：
Gambello, Michael J.
中科院分区：
文献类型：
--
作者：
Hernandez, Omar;Way, Sharon;Gambello, Michael J.
结节性硬化症是一种常染色体显性遗传病，由TSC1或TSC2基因突变引起。患有TSC的患者会出现各种器官系统的肿瘤，但脑部病理尤其严重。在小鼠中，TSC1或TSC2基因的常规基因破坏会导致有限的中枢神经系统病理。任何一种基因的纯合缺失都会导致中期死亡。为了避免传统TSC2基因敲除的纯合子致死性，我们在小鼠ES细胞中通过同源重组产生了TSC2基因的条件等位基因。纯合的TSC2(FLOX/FLOX)小鼠在许多典型的TSC影响的器官中与野生型完全相同，特别是大脑。利用这个TSC2(FLOX)等位基因，我们通过Cre重组产生了一个空等位基因。该等位基因将有助于研究适当的细胞和器官特异的Cre转基因小鼠的TSC病理。
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 gene. Patients afflicted with TSC develop tumors in various organ systems, but cerebral pathology is particularly severe. Conventional gene disruption of the Tsc1 or Tsc2 gene in mice cause limited central nervous system pathology. Homozygous deletion of either gene causes midgestation lethality. To circumvent the homozygous lethality of the conventional Tsc2 knockout we have generated a conditional allele of the Tsc2 gene by homologous recombination in mouse ES cells. The homozygous Tsc2(flox/flox) mice are identical to wildtype in many organs typically affected by TSC, especially the brain. Using this Tsc2(flox) allele we have generated a null allele using Cre recombination. This allele will be useful in investigating TSC pathology with appropriate cell and organ specific Cre-transgenic mice.