C57BL/6J-Kcnq2^Nmf134/J

Stock number: 004703
Product name: Nmf134
Research areas: Neurobiology Research, Sensorineural Research

Description

These mice carry an ENU-induced mutation characterized by a low threshold to electroconvulsive clonic seizures.

The Jackson Laboratory cannot guarantee that cryorecovery of strains from the discontinued NIH-funded Neuroscience Mutagenesis Facility (NMF) will be successful or that the anticipated phenotype or genotype will be obtained. The cryorecovery fee for this effort will not be refunded or prorated if the recovery is unsuccessful or is in any way unsatisfactory. Genotyping will be the responsibility of the Purchaser.

Detailed description

The mutants exhibit a low threshold to electroconvulsive clonic seizures, i.e. when stimulated transcorneally with the CC3 for minimal seizures in C57BL/6J mice (6.5 mA females, or 8.0 mA males), the majority responds not with minimal, but with intense, seizures. Therefore, NMF134 mutants might be useful for studying neurobiological mechanisms related to epilepsy.

This seizure phenotype was mapped as a binary dominant trait in 17 affected and 24 unaffected (C57BL/6J-Nmf134 x BALB/cByJ)F1 X BALB/cByJ N2 backcross mice. The apparent molecular interval was D2Mit148 - 2.5 cM - (Nmf134, D2Frk1=Kcnq2), with a peak LOD score of 4.2 at D2Frk1. Nmf134 is presently examined for mutations in Kcnq2.

Standard pathology work-up on two mutants that died during ECT testing (42 days of age) revealed no abnormalities; standard pathology performed on two additional mutants (68 days of age) that survived ECT testing also showed no abnormalities.

Development

This phenotypic deviant was generated by ethylnitrosourea (ENU) mutagenesis in C57BL/6J males (Stock No. 000664), in the Neuroscience Mutagenesis facility at The Jackson Laboratory. Mutagenized males were crossed to C57BL/6J females; G3 descendants of the mutagenized males were selected for neurological impairment.

Allele

Symbol: Cdh23^ahl
Name: age related hearing loss 1
MGI accession ID: MGI:3028349
Generation method: Spontaneous
Synonyms: Cdh23^753A; mdfw
Marker symbol: Cdh23
Marker name: cadherin 23 (otocadherin)
Marker synonyms: 4930542A03Rik; ahl; bob; CDHR23; mdfw; nmf112; nmf181; nmf252; PITA5; sals; USH1D
Chromosome: 10
Strain of origin: multiple strains
Molecular note: Genetic complementation tests have shown allelism between the mdfw (modifier of deaf waddler) locus and the ahl locus. Further analysis has shown this is caused by a G-to-A transition at coding nucleotide position 753 of Cdh23 (SNP rs257098870) at the 3' end of exon 7 (in ENSMUST00000073242). This hypomorphic allele changes splice donor site G-GT to A-GT, causing skipping of out-of-frame exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains in the encoded peptide and cause reduced message stability. Twenty-seven strains classified with ahl and carrying the 753A allele include: CD-1, RBF/DnJ, PL/J, AKR/J, RF/J, BALB/cBy, A/WySnJ, P/J, SENCARA/PtJ, DBA/1J, ALS/LtJ, C58/J, C57BLKS/J, 129P1/ReJ, C57BR/cd, SKH2/J, BUB/Bn, MA/MyJ, LP/J, 129X1/SvJ, NOR/LtJ, A/J, C57BL/6, NOD/LtJ, DBA/2J, ALR/LtJ, C57L/J. Strains classified with ahl that DO NOT carry this mutation include: 129S1/SvImJ, C3H/HeSnJ, I/LnJ, YBR/Ei, MRL/MpJ.

Allele

Symbol: Kcnq2^Nmf134
Name: neuroscience mutagenesis facility, 134
MGI accession ID: MGI:2661797
Generation method: Chemically induced (ENU)
Synonyms: Kcnq2^V182M
Marker symbol: Kcnq2
Marker name: potassium voltage-gated channel, subfamily Q, member 2
Marker synonyms: BFNC; DEE7; EBN; EBN1; ENB1; HNSPC; KCNA11; KQT2; KV7.2; Nmf134
Chromosome: 2
Strain of origin: C57BL/6J
Molecular note: A G-to-T transversion mutation in codon 182 results in the substitution of methionine for valine at this highly conserved position in the encoded protein.