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Phenotypes Associated with This Genotype
Genotype
MGI:5289775
Allelic
Composition
Olig2tm1(cre)Tmj/Olig2+
Smn1tm1Jme/Smn1tm1Msd
Grm7Tg(SMN2)89Ahmb/Grm7Tg(SMN2)89Ahmb
Genetic
Background
involves: 129 * 129P2/OlaHsd * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Grm7Tg(SMN2)89Ahmb mutation (34 available); any Grm7 mutation (125 available)
Olig2tm1(cre)Tmj mutation (0 available); any Olig2 mutation (46 available)
Smn1tm1Jme mutation (3 available); any Smn1 mutation (87 available)
Smn1tm1Msd mutation (37 available); any Smn1 mutation (87 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• about 70% of mutants survive to about 12 months of age
• about 30% of mutants die before 12 months of age

growth/size/body
• by the second day after birth, mutants show a 15% decrease in weight compared to controls

behavior/neurological
• mutants exhibit reduced grip strength, indicating weakness

muscle
• reduced muscle mass
• average size of mutant fibers is larger than controls
• muscle fiber loss occurs after P7
• atrophic fibers are seen in proximal (triceps) and distal (gastrocnemius) muscles
• small but significant proportion of muscle fibers exhibit centrally located nuclei, suggesting an ongoing regenerative process in muscle
• in an impaired righting ability test, mutants are noticeably weaker by postnatal day 2
• impaired righting reflex gradually subsides so that by the end of the second week of life, differences between mutants and controls are no longer seen
• however mutants continue to display weakness as adults

nervous system
• neonates exhibit a reduction of vGlut1 bouton numbers and their areas on motor neurons and a reduction of the total numbers of puncta in the ventral horn, indicating an aberration in the projection of proprioceptive sensory neurons onto ventral horns
• by P40, mutants exhibit an approximate 40% and 25% reduction in cervical and lumbar motor neurons, respectively
• the number of boutons juxtaposed against ChAT-positive motor neurons is reduced
• mean area of these synaptic boutons is reduced, suggesting an alteration in the synaptic coverage of the ventral horn motor neurons by Ia sensory terminals
• at the presynapse, neurofilament aggregates infiltrate nerve terminals and terminal arbors are swollen
• abnormal amounts of neurofilament protein persist in the nerve terminals of both proximal and distal muscles
• abnormal localization of synaptic vesicles in mutant terminals at P8 but no longer visible at P12
• NMJs in the triceps muscle are smaller, misshapen, and less mature than in controls or in mutant gastrocnemius muscle, indicating delayed maturation
• fragmented NMJs are seen in both triceps and gastrocnemius muscles
• at the postsynapse, more than 75% of gastrocnemial acetylcholine receptor clusters attain the normal pretzel-like conformation, but more than half of them appear fragmented and are measurably larger than in control NMJs
• acetylcholine receptor clusters of the triceps fail to attain the level of complexity as gastrocnemial muscle
• mutants exhibit severe defects of neuromuscular transmission at P8 but these defects are attenuated by P12 as disease progresses
• at P8, 100 Hz nerve stimulation of muscle is only able to produce 34% of the tension produced by direct muscle stimulation compared to 72% in controls, indicating that many junctions fail to active muscle fibers to threshold[?]
• at 100 Hz asynchronous release of calcium disappears at mutant NMJs undergoing numerous failures, suggesting there is little calcium entry into the nerve terminals during these events
• at P8, a decrease in the mean quantal content of the mutant junctions compared with controls, but at P10 and P12 mutant NJMs, the quantal content increases to control levels
• mean mEPP amplitude at mutant NMJs is 50-100% greater than at control junctions at P8, P10 and P12
• semitendinosus muscle of 3 month old mutants shows an increase in mEPP amplitude despite a decrease in input resistance, indicating that neuromuscular transmission defects persist at the NMJs of adults

skeleton

Mouse Models of Human Disease
DO ID OMIM ID(s) Ref(s)
Werdnig-Hoffmann disease DOID:13137 OMIM:253300
J:164292


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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last database update
11/12/2024
MGI 6.24
The Jackson Laboratory