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Mapping of a FEB 3 homologous febrile seizure locus on mouse chromosome 2 containing candidate genes Scn1a and Scn3a
Author(s) -
Hessel Ellen V. S.,
Lith Hein A.,
WolterinkDonselaar Inge G.,
Wit Marina,
Groot Koerkamp Marian J. A.,
Holstege Frank C. P.,
Kas Martien J. H.,
Fernandes Cathy,
Graan Pierre N. E.
Publication year - 2016
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/ejn.13420
Subject(s) - quantitative trait locus , genetics , candidate gene , biology , locus (genetics) , gene , chromosome , population , epilepsy , microbiology and biotechnology , medicine , environmental health , neuroscience
Febrile seizures ( FS ) are the most common seizure type in children. Recurrent FS are a risk factor for developing temporal lobe epilepsy later in life and are known to have a strong genetic component. Experimental FS ( eFS ) can be elicited in mice by warm‐air induced hyperthermia. We used this model to screen the chromosome substitution strain ( CSS ) panel derived from C57 BL /6J and A/J for FS susceptibility and identified C57 BL /6J‐Chr2 A /NaJ ( CSS 2), as the strain with the strongest FS susceptibility phenotype. The aim of this study was to map FS susceptibility loci and select candidate genes on mouse chromosome 2. We generated an F 2 population by intercrossing the hybrids ( F 1 ) that were derived from CSS 2 and C57 BL /6J mice. All CSS 2‐ F 2 individuals were genotyped and phenotyped for eFS susceptibility, and QTL analysis was performed. Candidate gene selection was based on bioinformatics analyses and differential brain expression between CSS 2 and C57 BL /6J strains determined by microarray analysis. Genetic mapping of the eFS susceptibility trait identified two significant loci: FS ‐ QTL 2a ( LOD ‐score 3.6) and FS ‐ QTL 2b ( LOD ‐score 6.2). FS ‐ QTL 2a contained 44 genes expressed in the brain at post natal day 14. Four of these ( Arl6ip6, Cytip, Fmnl2 Ifih1 ) contained a non‐synonymous SNP comparing CSS 2 and C57 BL /6J, six genes ( March7, Nr4a2, Gpd2, Grb14, Scn1a, Scn3a ) were differentially expressed between these strains. A region within FS ‐ QTL 2a is homologous to the human FEB 3 locus. The fact that we identify mouse FS ‐ QTL 2a with high FEB 3 homology is strong support for the validity of the eFS mouse model to study genetics of human FS.