Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome

被引:32
作者
Huebner, A
Mann, P
Rohde, E
Kaindl, AM
Witt, M
Verkade, P
Jakubiczka, S
Menschikowski, M
Stoltenburg-Didinger, G
Koehler, K
机构
[1] Tech Univ Dresden, Childrens Hosp, D-01307 Dresden, Germany
[2] Inst Mol Pharmacol, Dept Mol Genet, Berlin, Germany
[3] Univ Berlin, Sch Med, Charite, Dept Neuroped, Berlin, Germany
[4] Tech Univ Dresden, Dept Anat, D-8027 Dresden, Germany
[5] Max Planck Inst Mol Cell Biol & Genet, Dresden, Germany
[6] Otto Von Guericke Univ, Inst Human Genet, Magdeburg, Germany
[7] Tech Univ Dresden, Inst Clin Chem & Lab Med, D-8027 Dresden, Germany
[8] Univ Berlin, Sch Med, Charite, Inst Neuropathol, Berlin, Germany
关键词
D O I
10.1128/MCB.26.5.1879-1887.2006
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Triple A syndrome is a human autosomal recessive disorder characterized by adrenal insufficiency, achalasia, alacrima, and neurological abnormalities affecting the central, peripheral, and autonomic nervous systems. In humans, this disease is caused by mutations in the AAAS gene, which encodes ALADIN, a protein that belongs to the family of WD-repeat proteins and localizes to nuclear pore complexes. To analyze the function of the gene in the context of the whole organism and in an attempt to obtain an animal model for human triple A syndrome, we generated mice lacking a functional Aaas gene. The Aaas(-/-) animals were found to be externally indistinguishable from their wild-type littermates, although their body weight was on the average lower than that of wild-type mice. Histological analysis of various tissues failed to reveal any differences between Aaas(-/-) and wild-type mice. Aaas(-/-) mice exhibit unexpectedly mild abnormal behavior and only minor neurological deficits. Our data show that the lack of ALADIN in mice does not lead to a triple A syndrome-like disease. Thus, in mice either the function of ALADIN differs from that in humans, its loss can be readily compensated for, or additional factors, such as environmental conditions or genetic modifiers, contribute to the disease.
引用
收藏
页码:1879 / 1887
页数:9
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