Research article

Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice

Koji Sagane¹ , Kazuhiro Hayakawa² , Junko Kai¹ , Tomoko Hirohashi¹ , Eiki Takahashi¹ , Norimasa Miyamoto¹ , Mitsuhiro Ino¹ , Tohru Oki¹ , Kazuto Yamazaki¹ and Takeshi Nagasu¹

¹  Tsukuba Research Laboratories, Eisai Co., Ltd., Tokodai 5-1-3, Tsukuba, Ibaraki, 300-2635, Japan

²  Kawashima Research Laboratories, Eisai Co., Ltd., Kawashimatakehaya-machi 1, Kakamigahara, Gifu, 501-6195, Japan

author email corresponding author email

BMC Neuroscience 2005, 6:33doi:10.1186/1471-2202-6-33

Published:	6 May 2005

Abstract

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.

Conclusion

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.