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Abstract
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.
SUPPLEMENTAL MATERIAL
Supplemental material for this article may be found at http://mcb.asm.org/.
ACKNOWLEDGMENTS
This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan, by a grant from the 21st Century COE program of the Japan Society for the Promotion of Science, and by a grant from the Core Research Evolutional Science and Technology program of the Japan Science and Technology Corporation.
We thank Aiko Yonemitsu Yuki Satsuma of Osaka University for cell biology support, Yoshikazu Sado of Shigei Medical Research Institute for instruction regarding the rat iliac lymph node method, Yoshihide Hayashizaki of RIKEN for providing the EST clones, and Chikao Yutani and Munekazu Shigekawa of the National Cardiovascular Center and Yukihiko Kitamura of Osaka University for the pathology suggestions.