Overview

Also Known As: A53T α-synuclein transgenic line M83

M83 transgenic mice expresses the mutant human A53T alpha-synuclein under the direction of the mouse prion protein promoter. These mice may be useful in studying human neuronal alpha-synucleinopathies, such as familial Parkinson's Disease.

Donating Investigator

Virginia M Lee, University of Pennsylvania

Genetic overview

Genetic Background	Generation
	N?+N8F2 (2019-06-12 00:00:00)

Tg(Prnp-SNCA*A53T)83Vle

Allele Type
Transgenic (Inserted expressed sequence, Humanized sequence)

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Research Applications

Neurobiology Research
Sensorineural Research

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Base Price

Starting at:

$270.00 Domestic price for female 4-week

540.00 Domestic price for breeder pair

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Details

Detailed Description

Mice homozygous for the transgenic insert are viable and normal in size. These transgenic mice express human A53T variant alpha-synuclein (full-length, 140 amino acid isoform) under the direction of the mouse prion protein promoter. At eight months of age, some homozygous mice develop a progressively severe motor phenotype. Presentation of the phenotype may manifest at 14-15 months of age (on average). Lax grooming, weight loss and diminished mobility precede movement impairment, partial limb paralysis, trembling and inability to stand. Immunohistochemistry analysis of mutants between eight to 12 months of age reveals widely distributed alpha-synuclein inclusions, with dense accumulation in the spinal cord, brainstem, cerebellum and thalamus. The appearance of alpha-synuclein aggregate inclusions parallels the onset of the motor impairment phenotype. Axons and myelin sheaths exhibit progressive ultrastructural degeneration. Immunoelectron microscopy and biochemical analysis show the inclusions in neurons are comprised primarily of 10-16 nm fibrils of alpha-synuclein. The structure, location and onset of the inclusions seen in the mutant mice resemble characteristics seen in human neuronal alpha-synucleinopathies, such as familial Parkinson's Disease. In addition, mice exhibit impaired odor discrimination and detection beginning at 6 months of age. Mice hemizygous for the transgenic insert develop similar phenotypic traits, but onset occurs later, between 22 and 28 months of age. Homozygous mice have a high incidence of nonproductive matings.

Development

A transgenic construct containing the mouse prion protein promoter, its 5' and 3' untranslated regions and human alpha-synuclein A53T mutation cDNA sequence was injected into fertilized B6C3H mouse eggs. Transgenic animals are maintained on a mixed B6C3H background.

Expression Data

Expressed Gene	SNCA, synuclein alpha, human
Site of Expression

Control Suggestions

Approximate Controls

100010 B6C3F1/J

Additional Information

Considerations for Choosing Controls

Selected References

Giasson BI; Duda JE; Quinn SM; Zhang B; Trojanowski JQ; Lee VM. 2002. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4):521-33PubMed: 12062037 MGI: J:76657

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Genetics

Tg(Prnp-SNCA*A53T)83Vle

Allele Symbol: Tg(Prnp-SNCA*A53T)83Vle

Allele Name	transgene insertion 83, Virginia M-Y Lee
Allele Type	Transgenic (Inserted expressed sequence, Humanized sequence)
Allele Synonym(s)	transgene insertion 83, Virginia M-Y Lee; Tg(Prnp-SNCA*A53T)83Vle
Gene Symbol and Name	Tg(Prnp-SNCA*A53T)83Vle, transgene insertion 83, Virginia M-Y Lee
Gene Synonym(s)	A53T alpha-synuclein PRP; Tg(SNCA)83Vle; alphaS⁺; Tg(SNCA)83Vle; M83
Promoter	Prnp, prion protein, mouse, laboratory
Expressed Gene	SNCA, synuclein alpha, human
Strain of Origin	C57BL/6 x C3H
Chromosome	12
General Note	This line was originally designated M83. Line M91 was also generated.
Molecular Note	The transgene contains the mouse prion protein promoter, its 5' and 3' untranslated regions, and a human alpha synuclein cDNA sequence encoding a mutated protein with an Ala53Thr mutation. Transgene expression was detected in the cerebral cortex, spinal cord, and cerebellum. Transgene insertion occurred on Chr 12.
Mutations Made By	John Trojanowski, Dept. Pathology and Laboratory Med

Disease/Phenotype

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Parkinson's disease 1

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Neurobiology Research
- Neurodegeneration
- Parkinson's Disease
  - synuclein mutants
Sensorineural Research
- Olfaction

Mammalian Phenotype Terms by Genotype

The following phenotype relates to a compound genotype created using this strain

Genotype: Tg(Prnp-SNCAA53T)83Vle/Tg(Prnp-SNCAA53T)83Vle
involves: C3H * C57BL/6

behavior/neurological phenotype

abnormal gait
- reduced ambulation by 8 months of age

abnormal motor capabilities/coordination/movement

akinesia
- by 8 months of age, exhibit severe movement impairment with resistance to passive movement and partial paralysis of limbs, accompanied by periods of freezing of hindlimb

aphagia
- over time become unable to feed themselves

decreased grooming behavior
- by 8 months of age, grooming is neglected

hunched posture
- develop hunched backs by 8 months of age

impaired righting response
- unable to right themselves when placed on their sides

paresis
- partial paralysis of limbs is observed by 8 months of age, beginning at a hindleg but affecting all limbs within a few days

tremors
- temulous motion is seen in some mice, possibly related to attempted muscular activity

weakness
- eventually are unable to stand up and support their own body weight

growth/size/body region phenotype

weight loss
- by 8 months of age, begin to lose weight

mortality/aging

premature death

muscle phenotype

abnormal gastrocnemius morphology
- exhibit sparse neurogenic muscle atrophy

nervous system phenotype

abnormal myelination
- following axonal degeneration, the myelin sheath loosens and unravels

abnormal spinal nerve morphology
- endoneurial space is increased and axons are filled with vacuoles in the ventral roots of aged mice

alpha-synuclein inclusion body
- develop age-dependent intracytoplasmic neuronal alpha-synuclein inclusions that contain 10-16 nm wide fibrils similar to those seen in human alpha-synucleinopathies, with dense accumulation in the spinal cord, brainstem, cerebellum, and thalamus

axon degeneration
- significant axonal degeneration in aged mice

gliosis
- astrocytic gliosis

neurodegeneration
- show signs of neurodegeneration by 8 months of age and develop neurodegenerative disease within 16 months of age

Genotype: Tg(Prnp-SNCAA53T)83Vle/0
involves: C3H C57BL/6

behavior/neurological phenotype

abnormal motor capabilities/coordination/movement
- develop the severe and complex motor impairment leading to paralysis and death that is seen in homozygous transgenics, however onset is delayed from 16 months of age to 22-28 months of age

nervous system phenotype

abnormal nervous system morphology
- develop a similar neurodegenerative disease that is observed in homozygous transgenic mice, however onset is delayed from 16 months of age to 22-28 months of age
- mice develop some inclusions that are composed of both tau and alpha-synuclein

alpha-synuclein inclusion body
- mice exhibit formation of abundant alpha-synuclein inclusions

tau protein deposits
- about 25% of diseased mutants accumulate abundant tau-positive threads, grains and spheroids in regions of the pons, midbrain, and spinal core
- less frequent tau inclusions are present in another 25% of symptomatic mutants but none are seen in the rest 50% of diseased mutants
- rare perikaryal tau inclusions with morphology of a pre-tangle are seen

Genotype: Tg(Prnp-SNCAA53T)83Vle/?
B6;C3-Tg(Prnp-SNCAA53T)83Vle/J

behavior/neurological phenotype

abnormal habituation to a novel odor
- 6 and 10 month, but not 3 month, old mice do not sniff novel scent more than familiar scent

homeostasis/metabolism phenotype

decreased acetylcholinesterase activity
- decrease in acetylcholinesterase activity in olfactory bulb in 6 and 10 month old mice

nervous system phenotype

abnormal olfactory bulb glomerular layer morphology
- increase in dopaminergic neurons in olfactory bulb glomerular layer in 10 month old mice

abnormal olfactory bulb mitral cell layer morphology
- decreased numbers of cholinergic neurons are found in the olfactory bulb mitral layer in 10 month old mice

decreased neuron number
- decreased numbers of cholinergic neurons are found in the olfactory bulb mitral layer in 10 month old mice

increased dopaminergic neuron number
- increase in dopaminergic neurons in olfactory bulb glomerular layer in 10 month old mice

taste/olfaction phenotype

impaired olfaction
- time to locate buried food is increased in 6 and 10 month, but not 3 month, old mice as compared to wild-type

References

Giasson BI; Duda JE; Quinn SM; Zhang B; Trojanowski JQ; Lee VM. 2002. Neuronal alpha-synucleinopathy with severe movement disorder in mice expressing A53T human alpha-synuclein. Neuron 34(4):521-33PubMed: 12062037 MGI: J:76657

Additional - Tg(Prnp-SNCA*A53T)83Vle related

Technical Support

Contact Technical Support

Genotyping Protocols
- QPCR: Tg(SNCAcDNA)-qPCR
- Genotyping resources and troubleshooting
Dietary Information
- LabDiet® 5K52 formulation (6% fat)
Breeding Considerations

The strain is maintained as a hemizygote on the same background. Homozygous mice have a high incidence of nonproductive matings. Coat colors expected from breeding are agouti or black.
- Additional Breeding and Husbandry Support
Mating System
- Homozygote x Hemizygote
Citation
When using the A53T α-synuclein transgenic line M83 mouse strain in a publication, please cite the originating article(s) and include JAX stock #004479 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

AX11 (Maximum)

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Cryorecovery - Pricing

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	Hemizygous or non-carrier for Tg(Prnp-SNCA*A53T)83Vle

We will fulfill your order by providing at least two carriers for each strain ordered. The total number, sex, and genotypes provided will vary, although typically 8 or more animals are provided. Please check genotypes which will be recovered. While the genotypes of all animals produced will be communicated to you prior to scheduling shipment, the genotypes of animals provided may not reflect the mating scheme and genotypes described in the strain description. Animals are typically ready to ship in 11-14 weeks. If a second recovery is required to produce the minimum number of animals, then delivery time would increase to approximately 25 weeks. If we fail to produce animals of the correct genotype, you will not be charged. We cannot guarantee the reproductive success of mice shipped to your facility. If the mice are lost after the first three days (post-arrival) or do not produce progeny at your facility, a new order and fee will be necessary.

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Also Known As: A53T α-synuclein transgenic line M83

Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Approximate Controls

Additional Information

Selected References

Tg(Prnp-SNCA*A53T)83Vle

Allele Symbol: Tg(Prnp-SNCA*A53T)83Vle

Disease Terms

Characteristics of this human disease are associated with transgenes and other mutation types in the mouse.

Research Areas By Genotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Prnp-SNCA*A53T)83Vle/Tg(Prnp-SNCA*A53T)83Vleinvolves: C3H * C57BL/6

behavior/neurological phenotype

growth/size/body region phenotype

mortality/aging

muscle phenotype

nervous system phenotype

Genotype: Tg(Prnp-SNCA*A53T)83Vle/0involves: C3H * C57BL/6

behavior/neurological phenotype

nervous system phenotype

Genotype: Tg(Prnp-SNCA*A53T)83Vle/?B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J

behavior/neurological phenotype

homeostasis/metabolism phenotype

nervous system phenotype

taste/olfaction phenotype

References

Additional - Tg(Prnp-SNCA*A53T)83Vle related

Genotyping Protocols

Dietary Information

Breeding Considerations

Mating System

Citation

Animal Health Reports

Live Mouse

Breeder Pair

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

Additional Use Restrictions Apply

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Genotype: Tg(Prnp-SNCAA53T)83Vle/Tg(Prnp-SNCAA53T)83Vle
involves: C3H * C57BL/6

Genotype: Tg(Prnp-SNCAA53T)83Vle/0
involves: C3H C57BL/6

Genotype: Tg(Prnp-SNCAA53T)83Vle/?
B6;C3-Tg(Prnp-SNCAA53T)83Vle/J