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Human Molecular Genetics, 2002, Vol. 11, No. 15 1775-1784
© 2002 Oxford University Press

Osteopenia and male-specific sudden cardiac death in mice lacking a zinc transporter gene, Znt5

Koichi Inoue1,2, Koichi Matsuda1,3, Makoto Itoh4, Hiroshi Kawaguchi3, Hitonobu Tomoike4, Teruhiko Aoyagi5, Ryozo Nagai5, Masatsugu Hori2, Yusuke Nakamura1,* and Toshihiro Tanaka1

1Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Japan, 2Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, Japan, 3Department of Orthopedic Surgery Faculty of Medicine, University of Tokyo, Japan, 4First Department of Internal Medicine, Yamagata University School of Medicine, Yamagata, Japan and 5Department of Cardiovascular Medicine, University of Tokyo Graduate School of Medicine, Tokyo, Japan

Received April 10, 2002; Accepted May 24, 2002

We isolated a mammalian gene whose expression transiently increased in response to intimal denudation of rabbit aorta. It was identical to a gene encoding a zinc transporter, ZNT5, reported very recently by others. Mice deficient for this gene showed poor growth and a decrease in bone density due to impairment of osteoblast maturation to osteocyte. More than 60% of male null mice died suddenly because of the bradyarrhythmias. Analysis of gene-expression profiles in murine hearts by means of an oligonucleotide microarray disclosed that a subset of genes encoding immediate-early response factors (IEGs) and heat shock proteins (HSPs) were down-regulated in Znt5-null mice. These results indicate that Znt5 protein plays an important role in maturation of osteoblasts and in maintenance of the cells involved in the cardiac conduction system, partly owing to dysregulated expression of IEGs and HSPs.

* To whom correspondence should be addressed at: Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan. Tel: +81 354495372; Fax: +81 354495433; Email: yusuke{at}ims.u-tokyo.ac.jp


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