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Molecular and Cellular Biology, May 2005, p. 4138-4149, Vol. 25, No. 10
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.10.4138-4149.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

ABCA5 Resides in Lysosomes, and ABCA5 Knockout Mice Develop Lysosomal Disease-Like Symptoms{dagger}

Yoshiyuki Kubo,1,{ddagger} Sayaka Sekiya,1,2 Megumi Ohigashi,1,2 Chiemi Takenaka,4 Kyoko Tamura,4 Shigeyuki Nada,3 Tsuyoshi Nishi,1,5 Akitsugu Yamamoto,6 and Akihito Yamaguchi1,2,4*

Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Osaka 567-0047,1 Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871,2 Department of Oncogene Research, Research Institute for Microbial Diseases, Osaka University, Osaka 565-0871,3 CREST,4 PRESTO, JST, 4-1-8 Honcho Kawaguchi, Saitama,5 Nagahama Institute of Bio-Science and Technology, Shiga 526-0829, Japan6

Received 22 October 2004/ Returned for modification 9 December 2004/ Accepted 10 February 2005

ABCA5 is a member of the ABC transporter A subfamily, and a mouse orthologue (mABCA5) in newborn mouse brain and neural cells was identified by reverse transcription-PCR. Full-length cDNA cloning revealed that mABCA5 consists of 1,642 amino acid residues and that its putative structure is that of a full-type ABC transporter having two sets of six transmembrane segments and a nucleotide binding domain. Immunohistochemical studies revealed that mABCA5 is expressed in brain, lung, heart, and thyroid gland. A subcellular localization analysis showed that mABCA5 is a resident of lysosomes and late endosomes. Abca5–/– mice exhibited symptoms similar to those of several lysosomal diseases in heart, although no prominent abnormalities were found in brain or lung. They developed a dilated cardiomyopathy-like heart after reaching adulthood and died due to depression of the cardiovascular system. In addition, Abca5–/– mice also exhibited exophthalmos and collapse of the thyroid gland. Therefore, ABCA5 is a protein related to a lysosomal disease and plays important roles, especially in cardiomyocytes and follicular cells.

* Corresponding author. Mailing address: Department of Cell Membrane Biology, Institute of Scientific and Industrial Research, Osaka University, Ibaraki, Osaka 567-0047, Japan. Phone: 81-06-6879-8545. Fax: 81-06-6879-8549. E-mail: akihito{at}sanken.osaka-u.ac.jp.

{dagger} Supplemental material for this article may be found at http://mcb.asm.org/.

{ddagger} Present address: Department of Molecular Biopharmaceutics, Graduate School of Natural Science & Technology, Kanazawa University, Ishikawa 920-1192, Japan.

Molecular and Cellular Biology, May 2005, p. 4138-4149, Vol. 25, No. 10
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.10.4138-4149.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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