title: Behavioural and functional characterization of Kv10.1 (Eag1) knockout mice.
abstract: Kv10.1 (Eag1), member of the Kv10 family of voltage-gated potassium channels, is preferentially expressed in adult brain. The aim of the present study was to unravel the functional role of Kv10.1 in the brain by generating knockout mice, where the voltage sensor and pore region of Kv10.1 were removed to render non-functional proteins through deletion of exon 7 of the KCNH1 gene using the '3 Lox P strategy'. Kv10.1-deficient mice show no obvious alterations during embryogenesis and develop normally to adulthood; cortex, hippocampus and cerebellum appear anatomically normal. Other tests, including general health screen, sensorimotor functioning and gating, anxiety, social behaviour, learning and memory did not show any functional aberrations in Kv10.1 null mice. Kv10.1 null mice display mild hyperactivity and longer-lasting haloperidol-induced catalepsy, but there was no difference between genotypes in amphetamine sensitization and withdrawal, reactivity to apomorphine and haloperidol in the prepulse inhibition tests or to antidepressants in the haloperidol-induced catalepsy. Furthermore, electrical properties of Kv10.1 in cerebellar Purkinje cells did not show any difference between genotypes. Bearing in mind that Kv10.1 is overexpressed in over 70% of all human tumours and that its inhibition leads to a reduced tumour cell proliferation, the fact that deletion of Kv10.1 does not show a marked phenotype is a prerequisite for utilizing Kv10.1 blocking and/or reduction techniques, such as siRNA, to treat cancer.
authors: Department of Molecular Biology of Neuronal Signals, Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Str. 3, Göttingen 37077, Germany. rufarte@gwdg.de
authors: Roser
authors: R
authors: Ufartes
authors: Tomasz
authors: T
authors: Schneider
authors: Lena Sünke
authors: LS
authors: Mortensen
authors: Camino
authors: C
authors: de Juan Romero
authors: Klaus
authors: K
authors: Hentrich
authors: Hendrik
authors: H
authors: Knoetgen
authors: Vadim
authors: V
authors: Beilinson
authors: Wiebke
authors: W
authors: Moebius
authors: Victor
authors: V
authors: Tarabykin
authors: Frauke
authors: F
authors: Alves
authors: Luis A
authors: LA
authors: Pardo
authors: J Nicholas P
authors: JN
authors: Rawlins
authors: Walter
authors: W
authors: Stuehmer
mesh_terms: D000200:Action Potentials; D000661:Amphetamine / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage; D001522:Behavior, Animal / Q000187:drug effects; D001921:Brain / Q000378:metabolism; D002375:Catalepsy / Q000139:chemically induced / Q000188:drug therapy; D002531:Cerebellum / Q000378:metabolism; D055786:Gene Knockout Techniques; D023061:Gene Order; D018390:Gene Targeting; D005838:Genotype; D006220:Haloperidol / Q000009:adverse effects; D051379:Mice; D018345:Mice, Knockout; D010641:Phenotype; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics* / Q000378:metabolism*
chemical_list: D000928:Antidepressive Agents; C489605:Kcng3 protein, mouse; D024642:Potassium Channels, Voltage-Gated; D000661:Amphetamine; D006220:Haloperidol