About   Help   FAQ
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)
Citing These Resources
Funding Information
Warranty Disclaimer, Privacy Notice, Licensing, & Copyright
Send questions and comments to User Support.
last database update
10/29/2024
MGI 6.24
The Jackson Laboratory