In:
European Journal of Neuroscience, Wiley, Vol. 44, No. 11 ( 2016-12), p. 2950-2957
Kurzfassung:
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.
Materialart:
Online-Ressource
ISSN:
0953-816X
,
1460-9568
DOI:
10.1111/ejn.2016.44.issue-11
Sprache:
Englisch
Verlag:
Wiley
Publikationsdatum:
2016
ZDB Id:
2005178-5
SSG:
12
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