Phenotypes associated with this allele

• Allele Symbol: Snca^tm1Nbm
• Allele Name: targeted mutation 1, Robert L Nussbaum
• Allele ID: MGI:2389489
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Snca^tm1Nbm/Snca^tm1Nbm	involves: 129S6/SvEvTac * FVB/N	MGI:3723313
cn2	Slc6a3^tm1(cre)Lrsn/Slc6a3^+ Snca^tm1Nbm/Snca^tm1Nbm Tfam^tm1Lrsn/Tfam^tm1Lrsn	involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL	MGI:3702933
cx3	Snca^tm1Nbm/Snca^tm1Nbm Tg(Prnp-SNCA*A53T)AAub/Tg(Prnp-SNCA*A53T)AAub	involves: 129S6/SvEvTac * FVB/N	MGI:3723312
cx4	Snca^tm1Nbm/Snca^tm1Nbm Tg(SNCA*A30P)1Nbm/Tg(SNCA*A30P)1Nbm Tg(SNCA*A30P)2Nbm/Tg(SNCA*A30P)2Nbm	involves: 129S6/SvEvTac * FVB/N	MGI:4421410
cx5	Snca^tm1Nbm/Snca^tm1Nbm Tg(SNCA*A53T)1Nbm/Tg(SNCA*A53T)1Nbm Tg(SNCA*A53T)2Nbm/Tg(SNCA*A53T)2Nbm	involves: 129S6/SvEvTac * FVB/N	MGI:4421411

Genotype
MGI:3723313

hm1

• Allelic Composition: Snca^tm1Nbm/Snca^tm1Nbm
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

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

mortality/aging

mortality/aging ( J:124976 )

N • mice do not show decreased lifespan compared to wild-type controls

Genotype
MGI:3702933

cn2

• Allelic Composition: Slc6a3^tm1(cre)Lrsn/Slc6a3⁺; Snca^tm1Nbm/Snca^tm1Nbm; Tfam^tm1Lrsn/Tfam^tm1Lrsn
• Genetic Background: involves: 129S1/Sv * 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL

nervous system

neuronal intranuclear inclusions ( J:119515 )

• triple mutants show same phenotype as Tfam^tm1Lrsn, Slc6a3^tm1(cre)Lrsn mice; neuronal inclusions remain indicating that additional lack of Snca is not required for develoment of the Parkonsonian phenotype

Genotype
MGI:3723312

cx3

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

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

Genotype
MGI:4421410

cx4

• Allelic Composition: Snca^tm1Nbm/Snca^tm1Nbm; Tg(SNCA*A30P)1Nbm/Tg(SNCA*A30P)1Nbm; Tg(SNCA*A30P)2Nbm/Tg(SNCA*A30P)2Nbm
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

digestive/alimentary system

abnormal intestinal transit time ( J:156741 )

♀ • whole-gut transit time (WGTT) is significantly prolonged compared to controls starting at 3 months through 12 months of age;

abnormal large intestinal transit time ( J:156741 )

♀ • 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

behavior/neurological

behavior/neurological phenotype ( J:156741 )

♀N • mice show no motor abnormalities; rotarod latencies and distances traveled in open field tests are similar to controls at 6 and 12 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:156741

Genotype
MGI:4421411

cx5

• Allelic Composition: Snca^tm1Nbm/Snca^tm1Nbm; Tg(SNCA*A53T)1Nbm/Tg(SNCA*A53T)1Nbm; Tg(SNCA*A53T)2Nbm/Tg(SNCA*A53T)2Nbm
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

growth/size/body

growth/size/body region phenotype ( J:156741 )

N • body weigh does not differ from controls measured out to 18 months of age

behavior/neurological

impaired coordination ( J:156741 )

• 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

decreased locomotor activity ( J:156741 )

• 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

nervous system phenotype ( J:156741 )

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

N • striatal tissue dopamine and dopamine metabolite content are not different from controls at 11 and 18 months

N • no progressive loss of dopaminergic neurons in the substantia nigra, pars compacta (SNpc) is observed

N • olfaction and cardiac innervation by the autonomic nervous system are not affected by the transgenes

abnormal hippocampus morphology ( J:156741 )

• some dystrophic synapses are observed in rare instances at 12 or 22 months

alpha-synuclein inclusion body ( J:156741 )

• 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

abnormal digestive system physiology ( J:156741 )

• 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

abnormal intestinal transit time ( J:156741 )

• 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)

abnormal large intestinal transit time ( J:156741 )

• 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

cardiovascular system phenotype ( J:156741 )

N • no defects in autonomic cardiac innervation are detected

taste/olfaction

taste/olfaction phenotype ( J:156741 )

N • mice show no impairments in olfaction at 12 and 18 months of age

N • olfactory bulbs show no degeneration or protein aggregation at 12 and 18 months of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Parkinson's disease 1		DOID:0060367	OMIM:168601	J:156741