Phenotypes Associated with This Genotype

Genotype
MGI:3723312

• Allelic Composition: \Snca^tm1Nbm/\Snca^tm1Nbm; \Tg(Prnp-SNCA*A53T)AAub/\Tg(Prnp-SNCA*A53T)AAub
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

mortality/aging

premature death ( J:124976 )

• no mutants survive past 23 months, whereas controls show 60% survival at 24 months of age; mortality is significantly higher than in SCNA^tm1Nsb 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/body

slow postnatal weight gain ( J:124976 )

• 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

weight loss ( J:124976 )

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

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:124976 )

• dysfunction in a single hindlimb is usually the first pathological sign

abnormal reflex ( J:124976 )

• when suspended by the tail, mice do not show limb clasping, but limbs hang limply, and never are splayed as in wild-type

weakness ( J:124976 )

abnormal posture ( J:124976 )

• eventually, animals cannot support themselves and lay on their sides

abnormal gait ( J:124976 )

• in affected animals, knuckle-walking progressing to dragging of the hindlimbs is observed

short stride length ( J:124976 )

• at 17-18 months, mice show a shorter fore- and hindstride length

nervous system

gliosis ( J:124976 )

• marked gliosis is seen in affected mice, with none in controls

abnormal axon morphology ( J:124976 )

• sciatic nerves of affected animals show much greater damage and loss of axonal material

neuronal intranuclear inclusions ( J:124976 )

• presence of inclusion bodies (structureless smooth areas) is detected in spinal cords of some affected animals

abnormal spinal nerve morphology ( J:124976 )

• axons in dorsal and ventral roots in the spinal cord show heavy expression of SNCA compared to wild-type

abnormal ventral spinal root morphology ( J:124976 )

• in 19 month-old mice, more ventral root axons display empty sheaths or diminished, compressed contents than wild-type ventral roots

abnormal spinal cord ventral horn morphology ( J:124976 )

• 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

axon degeneration ( J:124976 )

• some degenerating axons are observed within intact myelin sheaths in the spinal cord

endocrine/exocrine glands

abnormal male preputial gland morphology ( J:124976 )

♂ • many animals' deaths are due to abscessed preputial gland cysts

skeleton

kyphosis ( J:124976 )

reproductive system

abnormal male preputial gland morphology ( J:124976 )

♂ • many animals' deaths are due to abscessed preputial gland cysts

renal/urinary system

abnormal male preputial gland morphology ( J:124976 )

♂ • many animals' deaths are due to abscessed preputial gland cysts

integument

abnormal male preputial gland morphology ( J:124976 )

♂ • many animals' deaths are due to abscessed preputial gland cysts

cellular

gliosis ( J:124976 )

• marked gliosis is seen in affected mice, with none in controls