Evaluation of HCN2 abnormalities as a cause of juvenile audiogenic seizures in Black Swiss mice.
Epilepsy is an often-debilitating disease with many etiologies. Genetic predisposition is common for many of the generalized epilepsy syndromes, and mutations in genes encoding neuronal ion channels are causative in many cases. We previously identified a locus for juvenile audiogenic monogenic seizures (jams1) in the Black Swiss mouse strain, delimited by the gene basigin (Bsg) and the marker D10Mit140. This region includes Hcn2, the gene encoding the hyperpolarization-activated cyclic nucleotide-gated channel subunit 2 (HCN2), an ion channel implicated in epilepsy. By sequencing genomic DNA, we found that Black Swiss mice have a single polymorphism in exon 2 within the Hcn2 gene. This single G/C to A/T base change alters the third position of a codon specifying alanine residue 293, without changing the predicted amino acid sequence. Furthermore, we found no detectable differences in HCN2 protein expression in the brains of Black Swiss mice, compared to control mice. We therefore reason that juvenile audiogenic seizures in Black Swiss mice are unlikely to be due to abnormalities of HCN2 channel function.
Davee Department of Neurology and Clinical Neurosciences, Northwestern University Medical School, 303 East Chicago Avenue, Ward Building 10-201, Chicago, IL 60611-3008, USA.
Minyoung
M
Shin
Dina
D
Simkin
Genn M
GM
Suyeoka
Dane M
DM
Chetkovich
D000367:Age Factors; D000375:Aging / Q000235:genetics; D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001921:Brain / Q000254:growth & development / Q000378:metabolism* / Q000503:physiopathology; D019556:COS Cells; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D020195:Epilepsy, Reflex / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017354:Point Mutation / Q000235:genetics; D015221:Potassium Channels; D009435:Synaptic Transmission / Q000235:genetics
C578711:Hcn2 protein, mouse; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels