Cre/loxP-Mediated inactivation of the bHLH transcription factor gene NeuroD/BETA2
Cre/loxP-Mediated inactivation of the bHLH transcription factor gene NeuroD/BETA2
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DOI：
10.1002/gene.20138
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发表时间：
2005-08-01
期刊：
影响因子：
1.5
通讯作者：
Nave, KA
中科院分区：
文献类型：
--
作者：
Goebbels, S;Bode, U;Nave, KA
Neurod/beta2是一种碱性螺旋-环-螺旋(BHLH)转录因子，在胰腺和神经系统发育过程中具有重要功能。由胰腺内分泌细胞分化障碍引起的糖尿病导致的神经缺失突变小鼠会在围产期死亡。此外，零突变体在小脑和海马颗粒细胞、内耳感觉神经元和视网膜光感受器细胞的形成中显示出严重的缺陷。对于空间和时间受限的Neurd基因失活，我们通过在Neurd编码区两侧加上loxP位点来产生条件突变小鼠。纯合子神经D(LoxP)突变小鼠是完全存活的，并表达正常水平的神经D mRNA和蛋白。在GABA(A)受体α6亚单位启动子的控制下，将神经(LoxP)小鼠与表达Cre重组酶的TG(mα6-Cre)B1LFR小鼠杂交，可使迁移后小脑颗粒细胞和部分脑干核团中的Neurd基因有效失活。Neuro(LoxP)小鼠突变体将成为研究神经系统和胰腺神经发育和成体功能的有价值的工具。
NeuroD/Beta2 is a basic helix-loop-helix (bHLH) transcription factor with important functions during development of the pancreas and the nervous system. NeuroD null mutant mice die perinatally due to diabetes caused by impaired differentiation of pancreatic endocrine cells. Additionally, null mutants display severe defects in the formation of cerebellar and hippocampal granule cells, inner ear sensory neurons, and retinal photoreceptor cells. For spatio-temporally restricted inactivation of the NeuroD gene, we generated conditional mouse mutants by flanking the NeuroD coding region with loxP sites. Homozygous NeuroD(loxP) mutant mice are fully viable and express normal levels of NeuroD mRNA and protein. Breeding Neuro(loxP) mice to Tg(m alpha 6-Cre)B1LFR mice that express Cre recombinase under control of the GABA(A) receptor alpha 6 subunit promoter resulted in efficient inactivation of the NeuroD gene in postmigratory cerebellar granule cells and a subset of brainstem nuclei. The Neuro(loxP) mouse mutant will be a valuable tool to study the developmental and adult function of NeuroD in nervous system and pancreas.