Kv1.1 null mice have enlarged hippocampus and ventral cortex

Ann-Sophie Persson,Eric Westman,Firoj Hossain Khan,Fu-Hua Wang,Christian Spenger,Catharina Lavebratt

doi:10.1186/1471-2202-8-10

Ann-Sophie Persson, Eric Westman + Show 4 more

Open Access

https://doi.org/10.1186/1471-2202-8-10

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Abstract

BackgroundMutations in the Shaker-like voltage-gated potassium channel Kv1.1 are known to cause episodic ataxia type 1 and temporal lobe epilepsy. Mice that express a malfunctional, truncated Kv1.1 (BALB/cByJ-Kv1.1mceph/mceph) show a markedly enlarged hippocampus and ventral cortex in adulthood.ResultsTo determine if mice lacking Kv1.1 also develop a brain enlargement similar to mceph/mceph, we transferred Kv1.1 null alleles to the BALB/cByJ background. Hippocampus and ventral cortex was then studied using in vivo 3D-magnetic resonance imaging and volume segmentation in adult Kv1.1 null mice, BALB/cByJ-Kv1.1mceph/mceph, BALB/cByJ-Kv1.1mceph/+, BALB.C3HeB -Kv1.1-/+ and wild type littermates. The Kv1.1 null brains had dramatically enlarged hippocampus and ventral cortex. Mice heterozygous for either the null allele or the mceph allele had normal-sized hippocampus and ventral cortex.ConclusionTotal absence of Kv1.1 can induce excessive overgrowth of hippocampus and ventral cortex in mice with a BALB/cByJ background, while mice with one wild type Kv1.1 allele develop normal-sized brains.

Highlights

Mutations in the Shaker-like voltage-gated potassium channel Kv1.1 are known to cause episodic ataxia type 1 and temporal lobe epilepsy
To establish if lack of functional Kv1.1 or the presence of the malfunctioning and truncated protein itself is the reason for the brain enlargement in mceph/mceph, we studied and compared hippocampus and ventral brain size using magnetic resonance imaging (MRI) in (1) animals with a complete lack of Kv1.1 (Kv1.1 null homozygotes), (2) animals that were lacking Kv1.1 in one allele but carried a functional Kv1.1 on the other allele (Kv1.1 null heterozygotes), (3) animals that had the truncating deletion in Kv1.1 in both (Kv1.1mceph/mceph, homozygotes) or only one allele
While the mceph mutation originated on BALB/cByJ, Kv1.1 null alleles were transferred through breeding from a C3HeB/FeJ background onto the background of theoretically 94% BALB/ cByJ and 6% C3HeB/FeJ

Summary

Results

To determine if mice lacking Kv1.1 develop a brain enlargement similar to mceph/ mceph, we transferred Kv1.1 null alleles to the BALB/cByJ background. Hippocampus and ventral cortex was studied using in vivo 3D-magnetic resonance imaging and volume segmentation in adult Kv1.1 null mice, BALB/cByJ-Kv1.1mceph/mceph, BALB/cByJ-Kv1.1mceph/+, BALB.C3HeB -Kv1.1-/+ and wild type littermates. The Kv1.1 null brains had dramatically enlarged hippocampus and ventral cortex. Mice heterozygous for either the null allele or the mceph allele had normal-sized hippocampus and ventral cortex

Background

Results and discussion

Methods

19. Racine RJ