期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 572, 期 -, 页码 112-117出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2021.07.095
关键词
SAMP8; Chromosome 12; Slc24a4 polymorphism; Loss of transporter activity; Ca2+ ion dysregulation; Alzheimer diseases
资金
- Takeda Science Foundation International Research Fellowship Program
- KAKENHI [07805510, 21373645]
- Basic Science and Platform Technology Program for Innovative Biological Medicine from Japan Agency for Medical Research and Development (AMED) [15657579]
- Research Program on Emerging and Re-emerging Infectious Diseases from AMED [19187977, 20333128]
- Toyama Pharmaceutical Valley Development Consortium
- Hokuriku Life Science Cluster
The study found a strong association of the Slc24a4 gene on chromosome 12 in the SAMP8 mouse strain with learning and memory deficits, with a single nucleotide polymorphism affecting calcium ion transporter activity. This finding may help clarify the importance of this ion exchanger in age-related cognitive dysfunction.
The senescence-accelerated mouse prone (SAMP) 8 strain exhibits age-related learning and memory deficits (LMD) at 2 months of age. We have found strong association of chromosome 12 locus with learning memory deficit (LMD) phenotype in SAMP8 strain. In the course of searching candidate gene, here we identified solute carrier family 24 sodium/potassium/calcium exchanger member 4 (Slc24a4) in SAMP8 chromosome 12 LMD possessing one single nucleotide polymorphism causing amino acid replacement of Threonine at 413 position with Methionine. Since SLC24A4 has been postulated as a candidate of late onset Alzheimer's diseases (LOAD), we further analyze the functional importance of this polymorphism. By expressing Slc24a4 protein in HEK293 cells, here we showed polymorphic SAMP8 type Slc24a4-T413 M causing significant loss of calcium ion (Ca2+ ) transporter activity in cells compared with that of wild type mouse (Slc24a4-WT). However, no study yet shows any functional association of human SLC24A4 polymorphism with the onset of LOAD pathogenesis. Thus, our present finding may further help to clarify the importance of this ion exchanger with age related cognitive dysfunction. (C) 2021 The Authors. Published by Elsevier Inc.
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