These mice carry an ENU-induced mutation characterized by seizures stemming from sensitivity to transcorneal stimulation.
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.Read More +
The C57BL/6J background strain is homozygous for the age related hearing loss mutation Cdh23ahl, which on this background causes progressive hearing loss with onset after 10 months of age.
nmf88 mutants are sensitive to transcorneal stimulation, i.e. when stimulated transcorneally with the CC3 for minimal electroconvulsive clonic seizures in C57BL/6J mice (6.5 mA for females, or 8.0 mA for males), the majority responds not with minimal, but with intense, grade 3 or higher, seizures*; they also show a low threshold for PTZ-induced generalized and tonic hindlimb seizures, i.e. following a sub-threshold dose of 40 mg/kg PTZ (s.c.), 4/4 homozygous males exhibited at least one generalized seizure and two of these progressed to tonic hindlimb extension seizures. Neither of two control males treated with the same dose displayed even a generalized seizure, consistent with prior results from other control animals. Although EEG recordings of two mice which extended over several hours showed no evidence of spontaneous seizures, because of their sensitivity to seizure induction, NMF88 mutants might be useful for studying neurobiological mechanisms related to epilepsy. NMF88 was mapped as a recessive mutation in the backcross (C57BL/6J-nmf88 x BALB/cByJ)F1 X C57BL/6J-nmf88. Linkage was found on distal Chromosome 2, but several mice carrying heterozygous marker genotypes throughout the region were affected, suggesting that the phenotype acted as a semi-dominant, at least in the mapping cross. In addition, there was a deficit of affected animals, suggesting that some do not survive to adulthood. Treating the phenotype as semi-quantitative, the most likely location was at the marker D2Frk1 (LOD 5.27) residing in the Kcnq2 gene (Yang et al., 2003), which is currently scanned for mutations. * (seizure grades: 0= no observable symptoms, 3= rearing, forelimb clonus and jaw clonus, 5= tonic hind limb extension seizure)
Standard pathology work-up on two mutants (49 or 292 days of age) showed degeneration of the inner nuclear layer of the peripheral retina in the older mouse. All other tissues appeared normal.
nmf88 was ENU induced in C57BL/6J and maintained on this same background. In 2004 embryos were generated for cryopreservation through in vitro fertilization using eggs from C57BL/6J females and sperm from homozygous males.
|Allele Name||neuroscience mutagenesis facility, 88|
|Allele Type||Chemically induced (ENU)|
|Gene Symbol and Name||nmf88, neuroscience mutagenesis facility, 88|
|Strain of Origin||C57BL/6J|
|Molecular Note||This phenotypic mutant was identified in an ENU mutagenesis screen.|
|Allele Name||age related hearing loss 1|
|Allele Synonym(s)||Cdh23753A; mdfw|
|Gene Symbol and Name||Cdh23, cadherin 23 (otocadherin)|
|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). This hypomorphic allele changes splice donor site G-GT to A-GT, causing frame skipping of exon 7. This is predicted to delete part of the 2nd and 3rd ectodomains 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.|