Analysis Tools|
Allele Symbol Allele Name Allele ID |
Mnx1tm4(cre)Tmj targeted mutation 4, Thomas M Jessell MGI:2447793 |
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| Summary |
19 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• compared with Gt(ROSA)26Sortm1(CAG-PLS3,-GFP)Bwir heterozygotes
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• mice exhibit reduced endplate size compared with Gt(ROSA)26Sortm1(CAG-PLS3,-GFP)Bwir heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• seven days after quadriceps femoris nerve crush, axon outgrowth from lesion site is significantly less than in wild-type
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• sciatic functional index (SFI), following sciatic nerve crush, is worse in mutant as compared to wild-type
• initial decline is similar, but recovery is slower and does not reach initial state of function after 35 days
• toe spreading is worse after crush as compared to wild-type
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• compound muscle action potential (CMAP) is reduced following sciatic nerve crush and does not fully recover
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• nerve conduction velocity (NCV) is reduced following sciatic nerve crush as compared to wild-type, but recovers by 35 days
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• regeneration of motor fibers is delayed at 14 days and 28 days following quadriceps femoris nerve crush as compared to wild-type
• reduced number of motor fibers at 14 days and 28 days following quadriceps femoris nerve crush as compared to wild-type
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• seven days after quadriceps femoris nerve crush, axon outgrowth from lesion site is significantly less than in wild-type
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• median survival of 12 days
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| N |
• neuromuscular junctions are similar to controls in the intercostal and triangularis sterni muscles
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• decrease in cardiac autonomic innervation
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• in L3-L5 spinal cord sections but not in the cervical or thoracic regions
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• by P9
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• end-stage mice display skipped or dropped beats
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• at P9-P11
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• at P9-P11
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| N |
• ambulatory throughout life
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• lateral instability of the hind limbs
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• significantly improved righting response
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Werdnig-Hoffmann disease | DOID:13137 |
OMIM:253300 |
J:183080 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice do not exhibit any obvious phenotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice have very few dorsal root ganglia neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination
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• mice have very few dorsal root ganglia neurons at brachial levels and increasingly more neurons progressing caudally undergo recombination
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal nerve conduction velocities and compound muscle action potentials
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• normal myelination of plantaris, quadriceps or saphenous nerves
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normalized muscle fiber size compared with Mnx1tm4(cre)Tmj heterozygotes
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| N |
• mice exhibit normalized endplate size compared with Mnx1tm4(cre)Tmj heterozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• loss of small diameter but not large diameter axons in lumbar ventral roots and in distal medial gastrocnemius nerve
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit an 80% decrease in dendrite branches, a 50% reduction in overall tree size, a 50% reduction in average dendrite length and a 15% reduction in the length of the longest dendrite compared to in wild-type mice
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• mice exhibit progressive degeneration of motor function without sensory loss
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• mice exhibit abnormal clasping of the legs and digits upon tail suspension at 6, but not 2, months of age
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• mice show a shorter latency to fall off the rotarod by 6 months of age
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• grip strength, measured across all 4 limbs, is reduced by 6 months of age
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• freely ambulating mice exhibit reductions in the percentage of overlapping footfalls by 8 months of age and lower frequency of diagonal contacts and compensatory increase in triagonal contacts by 6 months of age
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• copper concentrations are decreased in the lumbar spinal cords at 6 and 12 months of age but not at 2 months
• motor neuron cell bodies of 8 month old mice show an accumulation of copper
• however, total copper concentrations and iron concentrations in the liver and brain are normal and serum ceruloplasmin activity and blood hemoglobin are normal
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• mice show a decrease in muscle mass by 12 months of age
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• mice exhibit a progressive late-onset muscle atrophy
• gastrocnemius muscle shows a loss of muscle bundles and the presence of inclusion bodies at 12, but not 6, months of age
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• mice exhibit fewer motor neurons in the ventral horn by 12 months of age
• however, axonal diameter and myelin thickness of sciatic nerves is normal
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• symptomatic mice exhibit a decrease in the percentage of innervated neuromuscular junctions (NMJs) at 6 and 8 months which was further decreased by 12 months, indicating denervation of NMJs
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• gonadal fat content is elevated at 12 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| X-linked distal spinal muscular atrophy 3 | DOID:0111196 |
OMIM:300489 |
J:221066 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• some mice are stillborn while others survive into adulthood and are fertile
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• mice exhibit neurofilament-rich sprouts that extend beyond normally innervated endplates
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| N |
• diaphragms exhibit full innervation unlike in Phr1tm1.1Adia homozygotes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• average lifespan of mutants showing amyotrophic lateral sclerosis-like phenotypes is 10 months
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• average weight is slightly lower at early birth than in controls and this difference becomes more pronounced with age, with a significant weight difference after 8 weeks of age
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• while mutants show a peak of weight gain during 90-100 days of age, soon after this time, they begin to show weight loss
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• abnormal hind limb clasping is seen after 13 weeks of age
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• mutants show a deficiency in the rotarod test after 13 weeks of age
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• microglia activation is seen in the lateroventral lumbar spinal cord
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• more males than females develop amyotrophic lateral sclerosis-like phenotypes with a male/female ratio of 3:1
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• microglia activation is seen in the lateroventral lumbar spinal cord
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• in the spinal cord
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• accumulation of ubiquitinated proteins in the spinal cord motor neurons at 20 weeks of age
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• progressive loss of motor neurons, with a 10% decrease of spinal cord motor neurons at 10 weeks of age and a large loss of ChAT-positive motor neurons at 20 weeks of age
• 46% and 25% reduction in alpha and gamma motor neurons, respectively, in the lumbar regions of the spinal cord at 20 weeks of age
• more males than females develop amyotrophic lateral sclerosis-like phenotypes with a male/female ratio of 3:1
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• motor neuron loss, reactive astrocytosis, microglia activation and accumulation of polyubiquitinated proteins in the ventral horn
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• mutants exhibit kyphosis beginning at 20 weeks of age which becomes severe at 24 weeks
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• microglia activation is seen in the lateroventral lumbar spinal cord
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| amyotrophic lateral sclerosis type 10 | DOID:0060201 |
OMIM:612069 |
J:190254 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• 5-month-old mice show a reduction in body weight
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• mice develop motor defects by 5 months of age that become progressively more severe with age
• overt motoric defects recapitulate phenotypes for amyotrophic lateral sclerosis (ALS 3A)
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• swelling of axonal tips in motor neurons is apparent as early as 1 month after birth and becomes progressively more severe with age
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• mice show severe structural abnormalities of the neuromuscular junction (NMJ), including presynaptic fragmentation of the NMJ, axonal tip swellings, and massive axonal sprouting that are notable at 5 months of age
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• mice develop muscle atrophy by 5 months of age that becomes progressively more severe with age
• 5-month-old mice show highly atrophied thoracic musculature
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• mice develop kyphosis of the spine by 5 months of age that becomes progressively more severe with age
• severe kyphosis is due to atrophy and weakness of paraspinal muscles
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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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• mice lack motor neurons when examined from E12 to E16.9
(J:69623)
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• with cyanosis
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• increased number and length of secondary or intramuscular branches with tertiary and quaternary branches
• secondary branches are longer than in Lrp4tm1.1Line/Lrp4tm1.1Line Tg(ACTA1-cre)79Jme mice
• nerve terminals are fragmented in diaphragm
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• severely impaired formation
• almost undetectable in the diaphragm at E13.5
• fewer and smaller AChR clusters
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice exhibit normal neuromuscular synapse formation
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• absence of fusimotor nerve terminals
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• loss of small diameter but not large diameter axons in lumbar ventral roots and in distal medial gastrocnemius nerve
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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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