Mouse Genome Informatics
cx1
    Sncatm1Nbm/Sncatm1Nbm
Tg(Prnp-SNCA*A53T)AAub/Tg(Prnp-SNCA*A53T)AAub

involves: 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 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

growth/size
• 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
• 12-20% loss in body weight is observed ~2 weeks prior to onset of motor dysfunction in limbs

behavior/neurological
• dysfunction in a single hindlimb is usually the first pathological sign
• when suspended by the tail, mice do not show limb clasping, but limbs hang limply, and never are splayed as in wild-type
• eventually, animals cannot support themselves and lay on their sides
• in affected animals, knuckle-walking progressing to dragging of the hindlimbs is observed
• at 17-18 months, mice show a shorter fore- and hindstride length

nervous system
• marked gliosis is seen in affected mice, with none in controls
• sciatic nerves of affected animals show much greater damage and loss of axonal material
• presence of inclusion bodies (structureless smooth areas) is detected in spinal cords of some affected animals
• axons in dorsal and ventral roots in the spinal cord show heavy expression of SNCA compared to wild-type
• in 19 month-old mice, more ventral root axons display empty sheaths or diminished, compressed contents than wild-type ventral roots
• 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
• some degenerating axons are observed within intact myelin sheaths in the spinal cord

endocrine/exocrine glands
• many animals' deaths are due to abscessed preputial gland cysts (J:124976)

skeleton

reproductive system
• many animals' deaths are due to abscessed preputial gland cysts (J:124976)

renal/urinary system
• many animals' deaths are due to abscessed preputial gland cysts (J:124976)

integument
• many animals' deaths are due to abscessed preputial gland cysts (J:124976)


Mouse Genome Informatics
tg2
    Tg(Prnp-SNCA*A53T)AAub/Tg(Prnp-SNCA*A53T)AAub
involves: 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice show increased survival relative to SNCA-null transgenic animals, but survival is reduced relative to wild-type or SNCA-null mice


Mouse Genome Informatics
tg3
    Tg(Prnp-SNCA*A53T)AAub/Tg(Prnp-SNCA*A53T)AAub
involves: FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• up to 4 months of age, mutants perform better than controls on the accelerating rotating rod, but beyond 4 months, display progressive difficulties maintaining balance
• grip strength of forelimbs is significantly impaired (67 ponds) relative to controls (125 ponds)
• grip strength of forelimbs is significantly impaired (67 ponds) relative to controls (125 ponds)
• progressive reduction in rearing behavior is observed in animals at 6, 18, and 24 months of age, with notably decreased activity apparent at 3 months of age
• step length of transgenic animals is reduced relative to wild-type (1.9 cm vs 2.25 cm in wild-type)

nervous system
• signs such as ballooning and kinky, tortuous, or corkscrew shapes of neurites are observed
• signs such as ballooning and kinky, tortuous, or corkscrew shapes of neurites are observed
• at 7 months of age, such abnormalities are seen only occasionally in the neocortex and hippocampus, but are frequently seen in a dense network of neurites in the olfactory bulb