Mouse Genome Informatics
hm1
    Sncatm1Nbm/Sncatm1Nbm
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
N
• mice do not show decreased lifespan compared to wild-type controls (J:124976)


Mouse Genome Informatics
cn2
    Slc6a3tm1(cre)Lrsn/Slc6a3+
Sncatm1Nbm/Sncatm1Nbm
Tfamtm1Lrsn/Tfamtm1Lrsn

involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• 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


Mouse Genome Informatics
cx3
    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
cx4
    Sncatm1Nbm/Sncatm1Nbm
Tg(SNCA*A30P)1Nbm/Tg(SNCA*A30P)1Nbm
Tg(SNCA*A30P)2Nbm/Tg(SNCA*A30P)2Nbm

involves: 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• whole-gut transit time (WGTT) is significantly prolonged compared to controls starting at 3 months through 12 months of age; (J:156741)
• motility of distal colon is reduced in males compared to controls at 6 and 12 months (J:156741)
• 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 (J:156741)
• at 12 months of age, changes in stool production and water content are even more marked (J:156741)
• reduction in stool wet weigh results from a reduction in water content and reduction in the dry mass of stool output (J:156741)

behavior/neurological
N
• mice show no motor abnormalities; rotarod latencies and distances traveled in open field tests are similar to controls at 6 and 12 months (J:156741)

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 1, Autosomal Dominant; PARK1 168601 J:156741


Mouse Genome Informatics
cx5
    Sncatm1Nbm/Sncatm1Nbm
Tg(SNCA*A53T)1Nbm/Tg(SNCA*A53T)1Nbm
Tg(SNCA*A53T)2Nbm/Tg(SNCA*A53T)2Nbm

involves: 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
N
• body weigh does not differ from controls measured out to 18 months of age (J:156741)

behavior/neurological
• 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
• 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

nervous system
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 (J:156741)
• striatal tissue dopamine and dopamine metabolite content are not different from controls at 11 and 18 months (J:156741)
• no progressive loss of dopaminergic neurons in the substantia nigra, pars compacta (SNpc) is observed (J:156741)
• olfaction and cardiac innervation by the autonomic nervous system are not affected by the transgenes (J:156741)
• some dystrophic synapses are observed in rare instances at 12 or 22 months
• 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

digestive/alimentary system
• 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
• 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)
• 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

cardiovascular system
N
• no defects in autonomic cardiac innervation are detected (J:156741)

taste/olfaction
N
• mice show no impairments in olfaction at 12 and 18 months of age (J:156741)
• olfactory bulbs show no degeneration or protein aggregation at 12 and 18 months of age (J:156741)

Mouse Models of Human Disease
OMIM IDRef(s)
Parkinson Disease 1, Autosomal Dominant; PARK1 168601 J:156741