Phenotyping mouse chromosome substitution strains reveal multiple QTLs for febrile seizure susceptibility

Genes, Brain and Behavior - Tập 8 Số 2 - Trang 248-255 - 2009
Ellen V.S. Hessel1,2, Koen L.I. van Gassen1,2, Inge G. Wolterink‐Donselaar1, Peter J. Stienen3, Cathy Fernandes4, Jan H. Brakkee1, Martien J. Kas1, P.N.E. de Graan1
1Department of Neuroscience and Pharmacology, Rudolf Magnus Institute of Neuroscience, University Medical Center Utrecht
2these authors contributed equally to this work
3Department of Clinical Sciences of Companion Animals, Division Anesthesiology and Neurophysiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, the Netherlands
4Department Psychological Medicine and Psychiatry, Institute of Psychiatry, King’s College London, London, UK

Tóm tắt

Febrile seizures (FS) are the most common seizure type in children and recurrent FS are a risk factor for developing temporal lobe epilepsy. Although the mechanisms underlying FS are largely unknown, recent family, twin and animal studies indicate that genetics are important in FS susceptibility. Here, a forward genetic strategy was used employing mouse chromosome substitution strains (CSS) to identify novel FS susceptibility quantitative trait loci (QTLs). FS were induced by exposure to warm air at postnatal day 14. Video electroencephalogram monitoring identified tonic–clonic convulsion onset, defined as febrile seizure latency (FSL), as a reliable phenotypic parameter to determine FS susceptibility. FSL was determined in both sexes of the host strain (C57BL/6J), the donor strain (A/J) and CSS. C57BL/6J mice were more susceptible to FS than A/J mice. Phenotypic screening of the CSS panel identified six strains (CSS1, ‐2, ‐6 ‐10, ‐13 and ‐X) carrying QTLs for FS susceptibility. CSS1, ‐10 and ‐13 were less susceptible (protective QTLs), whereas CSS2, ‐6 and ‐X were more susceptible (susceptibility QTLs) to FS than the C57BL/6J strain. Our data show that mouse FS susceptibility is determined by complex genetics, which is distinct from that for chemically induced seizures. This is the first data set using CSS to screen for a seizure trait in mouse pups. It provides evidence for common FS susceptibility QTLs that serve as starting points to fine map FS susceptibility QTLs and to identify FS susceptibility genes. This will increase our understanding of human FS, working toward the identification of new therapeutic targets.

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Genes, Brain and Behavior

Tập 8 Số 2

248-255

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