Analysis Tools
mortality/aging
| N |
• mice do not show decreased lifespan compared to wild-type controls
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Allele Symbol Allele Name Allele ID |
Sncatm1Nbm targeted mutation 1, Robert L Nussbaum MGI:2389489 |
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| Summary |
5 genotypes
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• mice do not show decreased lifespan compared to wild-type controls
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• triple mutants show same phenotype as Tfamtm1Lrsn, Slc6a3tm1(cre)Lrsn mice; neuronal inclusions remain indicating that additional lack of Snca is not required for develoment of the Parkonsonian phenotype
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• no mutants survive past 23 months, whereas controls show 60% survival at 24 months of age; mortality is significantly higher than in SCNAtm1Nsb homozygotes or Tg(Prnp-SNCA*A53T)BAub homozygotes
• major cause of death is a late onset neuronopathy, with onset from 16 to 23 months
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• mice weigh same as controls at 12-13 months of age, but differ at 17-18 months (42.6 gm vs 48.5 g wt) and reach a weight plateau at this age whereas controls continue to gain weight to 2 years of age
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• 12-20% loss in body weight is observed ~2 weeks prior to onset of motor dysfunction in limbs
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• dysfunction in a single hindlimb is usually the first pathological sign
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• when suspended by the tail, mice do not show limb clasping, but limbs hang limply, and never are splayed as in wild-type
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• eventually, animals cannot support themselves and lay on their sides
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• in affected animals, knuckle-walking progressing to dragging of the hindlimbs is observed
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• at 17-18 months, mice show a shorter fore- and hindstride length
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• sciatic nerves of affected animals show much greater damage and loss of axonal material
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• presence of inclusion bodies (structureless smooth areas) is detected in spinal cords of some affected animals
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• axons in dorsal and ventral roots in the spinal cord show heavy expression of SNCA compared to wild-type
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• in 19 month-old mice, more ventral root axons display empty sheaths or diminished, compressed contents than wild-type ventral roots
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• perinuclear lipid deposits are observed in the cytoplasm of some motor neurons
• increased lysosomal activity is detected in spinal cord
• in thoracic ventral horns of affected animals, accumulation of Lamp1-positive structures is seen in many motor neuron cell bodies, along with occasional large vacuoles
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• some degenerating axons are observed within intact myelin sheaths in the spinal cord
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• many animals' deaths are due to abscessed preputial gland cysts
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• many animals' deaths are due to abscessed preputial gland cysts
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• many animals' deaths are due to abscessed preputial gland cysts
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• many animals' deaths are due to abscessed preputial gland cysts
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
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• whole-gut transit time (WGTT) is significantly prolonged compared to controls starting at 3 months through 12 months of age;
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• motility of distal colon is reduced in males compared to controls at 6 and 12 months
• amount of stool passed/unit time and stool water content are unchanged at 3 months of age but by 6 months these parameters are reduced to comparable degrees
• at 12 months of age, changes in stool production and water content are even more marked
• reduction in stool wet weigh results from a reduction in water content and reduction in the dry mass of stool output
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N |
• mice show no motor abnormalities; rotarod latencies and distances traveled in open field tests are similar to controls at 6 and 12 months
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease 1 | DOID:0060367 |
OMIM:168601 |
J:156741 | |
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| ♀ | phenotype observed in females |
| ♂ | phenotype observed in males |
| N | normal phenotype |
| N |
• body weigh does not differ from controls measured out to 18 months of age
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• males and females exhibit consistently reduced latency to fall beginning at 6 months; this persisted at 1 year of age and more pronounced at 18 months; endurance and coordination in the rotating rod test are abnormal
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• total distance traveled in the open field apparatus is reduced compared to controls at 6 months and remains abnormal at 18 months
• distance traveled decreases with age, showing reduced ambulatory distance traveled compared to controls at 12 and 18 months; reduction is generalized, not specific to a particular type of movement or region
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| N |
• dorsal motor nucleus of the vagus shows no abnormal alpha-synuclein aggregation and any widespread aggregates are not detected in brain homogenates of 5 and 18 month-old animals
• striatal tissue dopamine and dopamine metabolite content are not different from controls at 11 and 18 months
• no progressive loss of dopaminergic neurons in the substantia nigra, pars compacta (SNpc) is observed
• olfaction and cardiac innervation by the autonomic nervous system are not affected by the transgenes
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• some dystrophic synapses are observed in rare instances at 12 or 22 months
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• protein is present in tyrosine hydroxylase (TH)-immunoreactive neuronal cell bodies within myenteric and submucosal plexuses; varicose TH-positive terminals of noradrenergic sympathetic neurons
• most alpha-synuclein positive neurons, especially in the myenteric plexus are not coincident with TH immunostaining
• proteinase K-resistant alpha-synuclein aggregates are observed in the nuclear and perinuclear cytoplasm of enteric nervous system neurons in mice showing gastrointestinal motility dysfunction
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• proteinase K-resistant alpha-synuclein aggregates are observed in the nuclear and perinuclear cytoplasm of enteric nervous system neurons in mice showing gastrointestinal motility dysfunction
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• whole-gut transit time (WGTT) is prolonged compared to controls starting at 3 months and is markedly prolonged at 6 months persisting through 18 months of age; this phenotype does not differ between males and females in contrast to bead expulsion time (distal colonic motility)
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• motility of distal colon is reduced compared to controls with males showing around a 4-5 fold prolongation in expulsion compared to controls; reduction is exaggerated compared to females
• this phenotype is present at 3 months and persists through 18 months of age
• amount of stool passed/unit time and stool water content are unchanged at 3 months of age but by 6 months these parameters are reduced to comparable degrees
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| N |
• no defects in autonomic cardiac innervation are detected
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| N |
• mice show no impairments in olfaction at 12 and 18 months of age
• olfactory bulbs show no degeneration or protein aggregation at 12 and 18 months of age
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Mouse Models of Human Disease |
DO ID | OMIM ID(s) | Ref(s) | |
| Parkinson's disease 1 | DOID:0060367 |
OMIM:168601 |
J:156741 | |
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 04/16/2024 MGI 6.23 |
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