Family Identifier |
NMF88 |
Synonym(s) |
C57BL/6J-nmf88/J; JR#4656 |
Synopsis |
Low threshold to electroconvulsive minimal clonic seizures. |
Gene Symbol |
nmf88 (View MGI Record) |
Gene |
neuroscience mutagenesis facility88 |
Allele Symbol |
nmf88 (View MGI Record) |
Allele |
neuroscience mutagenesis facility88 |
Abnormal Assay(s) |
Assay: Electroconvulsive threshold (ECT)
Domain(s): Epilepsy
|
Phenotype Description |
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)
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Pathology Report |
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. |
HERITABILITY AND MAPPING INFORMATION
|
Background Strain |
C57BL/6J |
Heritability Mode |
Recessive |
Heritability Status |
Proven; 7 presumed heterozygous matings resulted in 12 affected mice in a total of 53 progeny. Additional matings have continued to produce affected mice. This ratio may represent an underestimate of penetrance since some of these mice were tested in the presence of valproate (100mg/kg) to prevent adverse effects of seizures. |
Chromosome |
2 |
Molecular Interval |
D2Mit263 - 16.8 cM - D2Mit148 - 2 cM - (nmf88, D2Frk1); D2Frkl: LOD=5.27 |
Map
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STATUS INFORMATION
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Mutant Status |
Cryopreserved Embryos
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Comments |
Please note: The majority of frozen NMF embryos is obtained through matings between homozygous (or heterozygous) mutant males and wild-type females; if recovery of mutants is requested, the mice will be shipped as soon as possible following wean without further phenotype or genotype testing. NMF embryos are supplied subject to the General Terms and Conditions of Sale posted at www.jaxmice.jax.org. For prices or further information, please inquire at srp@jax.org or nmf-mice@jax.org.
(12) NMF88 have been requested by and distributed to 1 investigator. |
Contact e-Mail Address |
nmf-mice@jax.org |