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.
Virginia M Lee, University of Pennsylvania
Genetic Background | Generation |
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N?+N8F5
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Allele Type |
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Transgenic (Inserted expressed sequence, Humanized sequence) |
Starting at:
$270.00 Domestic price for female 4-week |
540.00 Domestic price for breeder pair |
These M83 transgenic mice express human A53T variant alpha-synuclein (full-length, 140 amino acid isoform) under the direction of the mouse prion protein promoter.
Mice homozygous for the transgenic insert are viable, fertile and normal in size. 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. Homozygous mice have a high incidence of nonproductive matings. Aggression is observed, particularly in males, and may be due at least in part to the B6;C3H genetic background.
Mice hemizygous for the transgenic insert develop similar phenotypic traits, but onset occurs later, between 22 and 28 months of age. When hemizygotes are bred together, there may be some incidence of nonproductive matings (~20%). Aggression is observed, particularly in males, and may be due at least in part to the B6;C3H genetic background.
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.
When maintaining a live colony at The Jackson Laboratory, homozygous mice may be bred to hemizygous mice. Every ~10 generations, we breed transgenic mice to B6C3F1/J (Stock No. 100010). As of October 2018, we have performed a total of eight crosses to B6C3F1/J.
Expressed Gene | SNCA, synuclein alpha, human |
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Site of Expression |
Allele Name | transgene insertion 83, Virginia M-Y Lee |
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Allele Type | Transgenic (Inserted expressed sequence, Humanized sequence) |
Allele Synonym(s) | A53T alpha-synuclein PRP; alphaS+; M83; PrP-alpha-syn mice (line M83); Prp-alphaSynA53T; Tg(SNCA)83Vle |
Gene Symbol and Name | Tg(Prnp-SNCA*A53T)83Vle, transgene insertion 83, Virginia M-Y Lee |
Gene Synonym(s) | |
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 |
When maintaining a live colony at The Jackson Laboratory, homozygous mice may be bred to hemizygous mice. Every ~10 generations, we breed transgenic mice to B6C3F1/J (Stock No. 100010). As of October 2018, we have performed a total of eight crosses to B6C3F1/J.
Because aggression is frequently observed for mice on a B6;C3H genetic background, particularly in males, homozygous females bred to hemizygous males may be the preferred to the reciprocal. Coat colors expected from breeding are agouti or black.
Homozygous mice have a high incidence of nonproductive matings. Aggression is observed, particularly in males, and may be due at least in part to the B6;C3H genetic background.
Mice hemizygous for the transgenic insert develop similar phenotypic traits, but onset occurs later, between 22 and 28 months of age. When hemizygotes are bred together, there may be some incidence of nonproductive matings (~20%). Aggression is observed, particularly in males, and may be due at least in part to the B6;C3H genetic background.
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.
Service/Product | Description | Price |
---|---|---|
Hemizygous or non-carrier for Tg(Prnp-SNCA*A53T)83Vle |
Frozen Mouse Embryo | B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J Frozen Embryos | $2595.00 |
Frozen Mouse Embryo | B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J Frozen Embryos | $3373.50 |
Frozen Mouse Embryo | B6;C3-Tg(Prnp-SNCA*A53T)83Vle/J Frozen Embryos | $3373.50 |
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