TY - JOUR
T1 - A candidate gene of Alzheimer diseases was mutated in senescence-accelerated mouse prone (SAMP) 8 mice
AU - Akbor, Maruf Mohammad
AU - Kim, Juhyon
AU - Nomura, Mai
AU - Sugioka, Juno
AU - Kurosawa, Nobuyuki
AU - Isobe, Masaharu
N1 - Publisher Copyright:
© 2021 The Authors
PY - 2021/10/1
Y1 - 2021/10/1
N2 - 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.
AB - 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.
KW - Alzheimer diseases
KW - Ca ion dysregulation
KW - Chromosome 12
KW - Loss of transporter activity
KW - SAMP8
KW - Slc24a4 polymorphism
UR - http://www.scopus.com/inward/record.url?scp=85111728042&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2021.07.095
DO - 10.1016/j.bbrc.2021.07.095
M3 - 学術論文
C2 - 34364289
AN - SCOPUS:85111728042
SN - 0006-291X
VL - 572
SP - 112
EP - 117
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
ER -