Targeted disruption of the mouse phosphomannomutase 2 gene causes early embryonic lethality
Targeted disruption of the mouse phosphomannomutase 2 gene causes early embryonic lethality
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DOI：
10.1128/mcb.02391-05
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发表时间：
2006-08-01
影响因子：
5.3
通讯作者：
Koerner, Christian
中科院分区：
文献类型：
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作者：
Thiel, Christian;Luebke, Torben;Koerner, Christian
催化甘露糖-6-磷酸转化为甘露糖-1-磷酸的胞质酶磷酸甘露糖变位酶2（PMM 2）的突变引起最常见形式的先天性糖基化病症，称为CDG-Ia。它是一种遗传性多系统疾病，伴有严重的神经功能损害。为了研究CDG-Ia的病理生理学并研究可能的治疗方法，我们通过靶向破坏Pmm 2基因产生了CDG-Ia的小鼠模型。杂合子突变小鼠在发育、大体解剖和生育力方面表现正常。相反，在胚胎发育的第2.5至3.5天，Pmm 2-null等位基因的纯合胚胎被回收。这些结果表明，Pmm 2是小鼠早期发育所必需的。杂合子小鼠与野生型小鼠的交配实验可以进一步显示雌性Pmm 2无效等位基因的传递受损。
Mutations in the cytosolic enzyme phosphomannomutase.2 (PMM2), which catalyzes the conversion of mannose-6-phosphate to mannose-l-phosphate, cause the most common form of congenital disorders of glycosylation, termed CDG-Ia. It is an inherited multisystemic disease with severe neurological impairment. To study the pathophysiology of CDG-Ia and to investigate possible therapeutic approaches, we generated a mouse model for CDG-Ia by targeted disruption of the Pmm2 gene. Heterozygous mutant mice appeared normal in development, gross anatomy, and fertility. In contrast, embryos homozygous for the Pmm2-null allele were recovered in embryonic development at days 2.5 to 3.5. These results indicate that Pmm2 is essential for early development of mice. Mating experiments of heterozygous mice with wild-type mice could further show that transmission of the female Pmm2-null allele is impaired.