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Molecular and Cellular Biology, March 2006, p. 1879-1887, Vol. 26, No. 5
0270-7306/06/$08.00+0     doi:10.1128/MCB.26.5.1879-1887.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Mice Lacking the Nuclear Pore Complex Protein ALADIN Show Female Infertility but Fail To Develop a Phenotype Resembling Human Triple A Syndrome

Angela Huebner,^1* Philipp Mann,¹ Elvira Rohde,² Angela M. Kaindl,^1,3 Martin Witt,⁴ Paul Verkade,⁵ Sibylle Jakubiczka,⁶ Mario Menschikowski,⁷ Gisela Stoltenburg-Didinger,⁸ and Katrin Koehler¹

Children's Hospital, Technical University Dresden, Dresden, Germany,¹ Department of Molecular Genetics, Institute of Molecular Pharmacology, Berlin, Germany,² Department of Neuropediatrics, Charité, University Medical School, Berlin, Germany,³ Department of Anatomy, Technical University Dresden, Dresden, Germany,⁴ Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany,⁵ Institute of Human Genetics, Otto-von-Guericke University, Magdeburg, Germany,⁶ Institute of Clinical Chemistry and Laboratory Medicine, Technical University Dresden, Dresden, Germany,⁷ Institute of Neuropathology, Charité, University Medical School, Berlin, Germany⁸

Received 9 November 2005/ Accepted 6 December 2005

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.

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* Corresponding author. Mailing address: Children's Hospital, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. Phone: 49-351-458-2926. Fax: 49-351-458-4334. E-mail: angela.huebner{at}mailbox.tu-dresden.de.

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Molecular and Cellular Biology, March 2006, p. 1879-1887, Vol. 26, No. 5
0022-538X/06/$08.00+0     doi:10.1128/MCB.26.5.1879-1887.2006
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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