G2019S-LRRK2 transgenic mice have a minimal cytomegalovirus (CMV) enhancer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a mutated full length human leucine-rich repeat kinase 2 (LRRK2*G2019S) cDNA. These mice may be useful for studying Parkinson's Disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*G2019S expression.
Darren J Moore, Van Andel Research Institute
Valina Dawson, The Johns Hopkins University
G2019S-LRRK2 transgenic mice have a minimal cytomegalovirus (CMV) enhancer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a mutated full length human leucine-rich repeat kinase 2 (LRRK2*G2019S) cDNA. Hemizygotes are viable, fertile, and normal in size. The LRRK2 cDNA was modified to harbor the LRRK2*G2019S mutation associated with autosomal dominant, late-onset Parkinson's Disease (PD) originally identified in multiple Spanish families and patients with PD. LRRK2 protein, also known as Dardarin, contains multiple functional domains and may play a role in regulating alpha-synuclein-mediated neuropathology through modulating the intracellular trafficking and accumulation of SNCA protein. G2019S-LRRK2 is expressed throughout the olfactory bulb, cerebral cortex, hippocampus, striatum, cerebellum, and neurons of the substantia nigra pars compacta. G2019S-LRRK2 is also overexpressed (2.7-fold over endogenous) within tyrosine hydroxylase (TH)-positive dopaminergic neurons of the substantia nigra pars compacta. These transgenic mice display progressive nigral dopaminergic degeneration, in
addition to reduced complexity of cultured midbrain dopaminergic neurons. They also exhibit enhanced dopamine turnover in the olfactory bulb, as well as autophagic and mitochondrial abnormalities throughout the brain. These mice may be useful for studying PD pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*G2019S expression.
The G2019S-LRRK2 transgene was designed with a minimal cytomegalovirus (CMV) enhnacer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a full length human leucine-rich repeat kinase 2 (LRRK2) cDNA. LRRK2 cDNA was modified to harbor the LRRK2*G2019S mutation associated with autosomal dominant, late-onset Parkinson's disease. This transgene was microinjected into fertilized (C57BL/6J x C3H/HeJ) F1 oocytes. LRRK2*G2019S mice from founder line 340 were bred to C57BL/6J mice for at least 3 generations. Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J mice (Stock No. 000664) for at least one generation to establish the colony.
|Expressed Gene||LRRK2, leucine rich repeat kinase 2, human|
|Site of Expression|
|Allele Name||transgene insertion 340, Darren Moore|
|Allele Type||Transgenic (Inserted expressed sequence, Humanized sequence)|
|Allele Synonym(s)||Tg(PDGFB-LRRK2*G2019S)340Djmo; transgene insertion 340, Darren Moore|
|Gene Symbol and Name||Tg(PDGFB-LRRK2*G2019S)340Djmo, transgene insertion 340, Darren Moore|
|Promoter||PDGFB, platelet derived growth factor subunit B, human|
|Expressed Gene||LRRK2, leucine rich repeat kinase 2, human|
|Strain of Origin||(C57BL/6J x C3H/HeJ)F1|
|Molecular Note||The G2019S-LRRK2 transgene was designed with a minimal cytomegalovirus (CMV) enhancer and human platelet derived growth factor, B polypeptide (PDGFB) promoter/enhancer elements driving expression of a full length human leucine-rich repeat kinase 2 (LRRK2) cDNA. LRRK2 cDNA was modified by targeted mutation of the LRRK2 locus to harbor the LRRK2*G2019S mutation associated with autosomal dominant, late-onset Parkinson's disease. Line 340 was generated.|
|Mutations Made By|| |
Darren Moore, Van Andel Research Institute
When maintaining a live colony, hemizygous mice may be bred to wildtype (noncarrier) mice from the colony.
When using the G2019S-LRRK2 mouse strain in a publication, please cite the originating article(s) and include JAX stock #016575 in your Materials and Methods section.
|Hemizyous or Non Carrir for Tg(PDGFB-LRRK2*G2019S)340Djmo|
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.
Cryorecovery to establish a Dedicated Supply for greater quantities of mice. Mice recovered can be used to establish a dedicated colony to contractually supply you mice according to your requirements. Price by quotation.
|Frozen Mouse Embryo||$2,595.00 per straw or vial|
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