Analysis Tools|
Allele Symbol Allele Name Allele ID |
Smn1tm1Jme targeted mutation 1, Judith Melki MGI:2384151 |
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| Summary |
6 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• about 70% of mutants survive to about 12 months of age
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• about 30% of mutants die before 12 months of age
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• by the second day after birth, mutants show a 15% decrease in weight compared to controls
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• mutants exhibit reduced grip strength, indicating weakness
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• reduced muscle mass
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• average size of mutant fibers is larger than controls
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• muscle fiber loss occurs after P7
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• 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
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• 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
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• 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
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• by P40, mutants exhibit an approximate 40% and 25% reduction in cervical and lumbar motor neurons, respectively
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• 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
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• 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
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• 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
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• 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
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:164292 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mutants die at an average of 31 days of age
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• progressive degeneration of motor nerves beginning at 20 days of age, with about 35% loss at 30 days in the phrenic nerve and about 45% in the facial nerve
• progressive degeneration is also seen in the trochlear nuclei and in the motoneurons of the spinal cord
• however, no loss of trigeminal or hypoglossal motoneurons is observed
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• progressive degeneration of the facial nerve such that at 30 days, 45% loss is observed
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• progressive degeneration of the phrenic nerves such that at 30 days, 35% loss is observed
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• progressive axon degeneration that begins at 20 days of age
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• mutants exhibit motor defects at two weeks of age
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• mutants exhibit weight loss at two weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:89836 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• extremely reduced life expectancy, dying at a mean age of 25 days
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• severe motor defect evident at 2 weeks of age
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• abnormal posture of the hindlimbs
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• presence of groups of atrophic muscle fibers and angular fibers intermixed with normal-size fibers
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• severe hypotonia characterized by a defect of flexor muscles of the limbs and neck when suspended on a horizontal thread
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• pronounced morphological changes of nuclei of motor neurons
• the presence of indentations of the nuclear membrane
• no significant loss of motor neurons of the anterior horns was detected in 2-weeks old mutant mice
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• presence of a marked extrajunctional labeling of acetylcholine receptors indicating a denervation of skeletal muscle of neurogenic orgin
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:61396 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• extremely reduced life expectancy, dying at a mean age of 33 days
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• in 4 weeks old mutant mice
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• reduced spontaneous and induced motor activity after 3 weeks of age
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• infiltration of connective tissue with mononuclear cells, and regenerating myocytes in 4-weeks-old mutant mice
• the morphology of skeletal muscle from mutant mice was similar to that of control at 3 weeks of except the presence of some rare necrotic muscle fibers surrounded by mononuclear cell infiltration
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• excessive variation in fiber size
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• large central nuclei in 4-weeks-old mutant mice
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• in 4-weeks-old mutant mice
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• based on immunological examination, mutant mice display destabilization of the sarcolemma indicated by increased serum creatine kinase activity, abnormal uptake of a membrane impermeant molecule, and patchy or lacking dystrophin
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| N |
• the morphology of motor neurons was similar to that of control and no significant loss of motor neurons of the anterior horns was detected in mutant mice at 4 weeks of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:67884 | |
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 |
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