Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice.
BACKGROUND
ADAM22 is a member of the ADAM gene family, but the fact that it is expressed only in the nervous systems makes it unique. ADAM22's sequence similarity to other ADAMs suggests it to be an integrin binder and thus to have a role in cell-cell or cell-matrix interactions. To elucidate the physiological functions of ADAM22, we employed gene targeting to generate ADAM22 knockout mice.


RESULTS
ADAM22-deficient mice were produced in a good accordance with the Mendelian ratio and appeared normal at birth. After one week, severe ataxia was observed, and all homozygotes died before weaning, probably due to convulsions. No major histological abnormalities were detected in the cerebral cortex or cerebellum of the homozygous mutants; however, marked hypomyelination of the peripheral nerves was observed.


CONCLUSIONS
The results of our study demonstrate that ADAM22 is closely involved in the correct functioning of the nervous system. Further analysis of ADAM22 will provide clues to understanding the mechanisms of human diseases such as epileptic seizures and peripheral neuropathy.
Sagane
Koji
K
Tsukuba Research Laboratories, Eisai Co., Ltd., Tokodai 5-1-3, Tsukuba, Ibaraki, 300-2635, Japan. k-sagane@hhc.eisai.co.jp
Hayakawa
Kazuhiro
K
Kai
Junko
J
Hirohashi
Tomoko
T
Takahashi
Eiki
E
Miyamoto
Norimasa
N
Ino
Mitsuhiro
M
Oki
Tohru
T
Yamazaki
Kazuto
K
Nagasu
Takeshi
T
D051722:ADAM Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001259:Ataxia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D005260:Female; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics / Q000502:physiology*; D010525:Peripheral Nerves / Q000378:metabolism / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D009419:Nerve Tissue Proteins; D051722:ADAM Proteins; C121258:Adam22 protein, mouse