Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice
Chondrodysplasia and neurological abnormalities in ATF-2-deficient mice
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DOI：
10.1038/379262a0
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发表时间：
1996-01-18
期刊：
影响因子：
64.8
通讯作者：
Glimcher, LH
中科院分区：
文献类型：
--
作者：
Reimold, AM;Grusby, MJ;Glimcher, LH
激活转录因子-2(ATF-2)是一种碱性亮氨酸拉链蛋白，其DNA靶序列是分布广泛的cAMP反应元件(Cre)。我们在这里报道，携带ATF-2胚系突变的小鼠表现出ATF-2的独特作用，其他ATF/CREB家族成员没有复制。突变小鼠出生后的生存能力和生长能力下降，与人类软骨发育不良类似，在骨骺板处出现软骨内成骨缺陷。这些动物有共济失调的步态、多动症和听力下降。脑内小脑浦肯野细胞减少，前庭感觉器萎缩，脑室增大。与CREBα/Delta缺陷小鼠的主要缺陷是长时程增强不同，ATF-2突变小鼠的广泛异常表明，它对骨骼和中枢神经系统的发育是绝对必要的，并最大限度地诱导带有CRE位点的选择基因，如E-选择素。
ACTIVATING transcription factor-2 (ATF-2) is a basic region leucine zipper protein whose DNA target sequence is the widely distributed cAMP response element (CRE). We report here that mice carrying a germline mutation in ATF-2 demonstrated unique actions of ATF-2 not duplicated by other ATF/CREB family members. Mutant mice had decreased postnatal viability and growth, with a defect in endochondral ossification at epiphyseal plates similar to human hypochondroplasia. The animals had ataxic gait, hyperactivity and decreased hearing. In the brain, there were reduced numbers of cerebellar Purkinje cells, atrophic vestibular sense organs and enlarged ventricles. Unlike CREB alpha/delta-deficient mice whose main defect is in longterm potentiation, the widespread abnormalities in ATF-2 mutant mice demonstrate its absolute requirement for skeletal and central nervous system development, and for maximal induction of select genes with CRE sites, such as E-selectin.