Mice lacking the nuclear pore complex protein ALADIN show female infertility but fail to develop a phenotype resembling human triple A syndrome.
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.
Huebner
Angela
A
Children's Hospital, Technical University Dresden, Fetscherstrasse 74, 01307 Dresden, Germany. angela.huebner@mailbox.tu-dresden.de
Mann
Philipp
P
Rohde
Elvira
E
Kaindl
Angela M
AM
Witt
Martin
M
Verkade
Paul
P
Jakubiczka
Sibylle
S
Menschikowski
Mario
M
Stoltenburg-Didinger
Gisela
G
Koehler
Katrin
K
D000224:Addison Disease / Q000209:etiology* / Q000235:genetics; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D001835:Body Weight / Q000235:genetics; D004195:Disease Models, Animal; D004931:Esophageal Achalasia / Q000209:etiology* / Q000235:genetics; D005260:Female; D006728:Hormones / Q000378:metabolism; D006801:Humans; D007247:Infertility, Female / Q000235:genetics*; D007668:Kidney / Q000473:pathology / Q000648:ultrastructure; D007766:Lacrimal Apparatus Diseases / Q000209:etiology* / Q000235:genetics; D008099:Liver / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins; D009422:Nervous System Diseases / Q000209:etiology / Q000235:genetics; D022022:Nuclear Pore / Q000648:ultrastructure; D028861:Nuclear Pore Complex Proteins; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D013577:Syndrome
C416506:AAAS protein, human; D006728:Hormones; D009419:Nerve Tissue Proteins; D028861:Nuclear Pore Complex Proteins; D011506:Proteins