Possible involvement of Hcn1 ion channel in learning and memory dysfunction in SAMP8 mice

• Published in: Biochemical and biophysical research communications 2013-11, Vol.441 (1), p.25-30
• Main Authors: Akbor, Maruf Mohammad, Tomobe, Koji, Yamada, Tomomi, Kim, Juhyon, Mano, Hiroki, Kurosawa, Nobuyuki, Sasaki, Kazuo, Nomura, Yasuyuki, Isobe, Masaharu
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Analysis of Variance; Animals; Chromosome 13; Chromosomes, Mammalian - genetics; Crosses, Genetic; Female; Genetic Association Studies; Green Fluorescent Proteins - metabolism; Hcn1; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - chemistry; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels - metabolism; Learning; Learning and memory deficiency; Male; Memory Disorders - metabolism; Memory Disorders - physiopathology; Mice; Mice, Inbred Strains; Molecular Sequence Data; Patch-Clamp Techniques; Peptides - metabolism; Plasmids - metabolism; Potassium Channels - chemistry; Potassium Channels - metabolism; QTL analysis; Quantitative Trait Loci - genetics; RNA-seq analysis; SAMP8
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2013.09.145

•264 F2 intercross SAMP8 × JF1 mice were used for QTL analysis.•Hcn1 gene was identified out of 29 genes in the LMD region on chromosome 13 through RNA-seq and micro array analysis.•P2A-based bicistronic plasmids were constructed for stoichiometric production of GFP and Hcn1.•Hcn1 channel ion conductivity was found significantly lower in SAMP8 compared to JF1.•The low ion conductivity of SAMP8 type Hcn1 may be associated with learning and memory deficiency. The senescence-accelerated mouse prone 8 (SAMP8) strain exhibits age-related learning and memory deficits (LMD) at 2months of age. Combined linkage analysis of 264 F2 intercross SAMP8 × JF1 mice and RNA-seq analysis identified Hcn1 gene out of 29 genes in the LMD region on chromosome 13. Hcn1 in SAMP8 strain showed 15 times less polyglutamine repetition compared to Japanese fancy mouse 1 (JF1). Whole cell patch clamp analysis showed that Hcn1 ion conductivity was significantly lower in SAMP8 compared to that of JF1, which may be associated with learning and memory deficiency.