Family Identifier |
NMF249 |
Synonym(s) |
C57BL/6J-nmf249/J; JR#5013 |
Synopsis |
The mutants are small and develop an unsteady gait. |
Gene Symbol |
Nmf249 (View MGI Record) |
Gene |
Neuroscience mutagenesis facility249 |
Allele Symbol |
Nmf249 (View MGI Record) |
Allele |
Neuroscience mutagenesis facility249 |
Abnormal Assay(s) |
Assay: Overt movement/posture
Domain(s): Movement/Neuromuscular Function
; Visible Mutants
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Phenotype Description |
Mutant mice are smaller than their littermates and develop an unsteady gait about 3 weeks of age (average 3.5weeks of age +/-0.5, n=22). The mice fail to thrive and die between 4-8 weeks of age. Males and females are affected and do not live long enough to mate normally. Although the NMF249 mutation arose in an ENU mutagenized family, it is most likely a spontaneous mutation. The parents showed no overt phenotype and produced only 1 affected mouse in a total of 24 progeny. However, when this animal was mated to a wild-type male (using ovarian transplants), half the offspring was affected, suggesting that a spontaneous dominant mutation may have occurred. Ratios from subsequent matings are consistent with a fully penetrant dominant mutation. In vitro fertilization was attempted using sperm from a six-week-old mutant, however the yield was not sufficient to maintain the colony, and ovarian transplants (OTs) are required to maintain a colony.
(View video)
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Pathology Report |
The mice have a distal neuropathy in motor neurons with retracting axons (Figure 1) and poorly innervated or denervated neuromuscular junctions (Figure 2) visualized through immunohistochemistry (Figures 1 and 2: confocal images 100x) of neuromuscular junctions; green labeling indicates the presence of neurofilament protein in axons (SMI31) and synaptic vesicle proteins at motor terminals (SV2); red labeling indicates ACh receptors visualized with rhodamine-labeled alpha-bungarotoxin; yellow color reveals the overlay of the presynaptic nerve with the motor terminal arborization). Large diameter myelinated fibers are absent and a significant number of unidentified cells is evident in the sciatic nerve of affected mice (Figure 3). No defects have been observed in the CNS.
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HERITABILITY AND MAPPING INFORMATION
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Background Strain |
C57BL/6J |
Heritability Mode |
Dominant |
Heritability Status |
Proven; 4 matings between C57BL/6J and affected mice (using OTs) produced 23 affected mice in a total of 56 progeny.
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Chromosome |
6 |
Molecular Interval |
D6Mit183 - 3.7 cM - (Nmf249, D6Mit188, D6Mit361) - 15.9 cM - D6Mit132; linkage: D6Mit183 - LOD = 6.3; D6Mit188 - LOD = 8.1 |
Map
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STATUS INFORMATION
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Mutant Status |
Cryopreserved Embryos
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Comments |
(10) NMF249 have been requested by and distributed to 1 investigator.
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Contact e-Mail Address |
nmf-mice@jax.org |