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| These mice contain a mutation designed to replace gene function of the endogenous mouse Pink1 gene with the loss-of-function mutation, G309D, and a loxP-flanked neomycin resistance cassette (neo). These mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death. | |||||||||||||||
- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
Strain Information
Former Names 129-Pink1tm1Aub/J (Changed: 27-JUL-11 ) Type Coisogenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Mating System Homozygote x Homozygote (Female x Male) 14-NOV-11 Species laboratory mouse Generation F?+F4 (03-DEC-12)
Generation DefinitionsDonating Investigator Georg Auburger, University Medical School Description
These mice contain a mutation designed to replace gene function of the endogenous mouse Pink1 gene with the loss-of-function mutation, G309D, and a loxP-flanked neomycin resistance cassette (neo). Mice homozygous for Pink1-/- are viable and fertile. Mice with this mutation carry the same loss-of-function mutation found in early-onset PARK6-linked Parkinson's disease (PD). Unlike other PD models, these mice lack peripheral paralysis, and exhibit normal motor performance, coordination, anxiety, and lifespan. They also lack lewy bodies and have reduced expression of α-synuclein mRNA. As these mice age they exhibit a progressive reduction of weight, a reduction of locomotor activity, and abnormal dopamine levels. These mice show increasing mitochondrial dysfunction resulting in impaired neural activity similar to PD, in absence of overt neuronal death.Development
The targeting construct contains exon 5 of the mouse PTEN induced putative kinase 1 (Pink1) gene. Nucleotide 8343 in exon 5 was changed from a G to an A, reflecting the loss-of-function mutation, G309D, found in early-onset PARK6-linked Parkinson's Disease (PD). The targeting vector also contains a loxP-flanked neomycin resistance cassette (neo). This targeting construct, designed to replace exons 5 of the mouse Pink1 gene, was electroporated into 129/SvEv-derived embryonic stem (ES) cell line. Correctly targeted ES cells were injected into blastocysts. The resulting chimeric mice were bred to C57BL/6 mice and the colony was maintained on a mixed B6;129 background. Upon arrival at The Jackson laboratory, mice were bred to 129S1/SvImJ inbred mice (Stock No. 002448) for at least one generation.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
Related Strains
Parkinson's Disease Models
View Parkinson's Disease Models (109 strains)
017678 FVB;129-Pink1tm1Aub Tg(Prnp-SNCA*A53T)AAub/J
017946 B6.129S4-Pink1tm1Shn/J
Additional Web Information
Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.
Phenotype
Phenotype Information
- Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).
Parkinson Disease 6, Autosomal Recessive Early-Onset; PARK6
assigned by genotype
Pink1tm1Aub/Pink1tm1Aub
involves: 129S/SvEv
- nervous system phenotype
- *normal* nervous system phenotype
- decreased dopamine level
- decreased dopamine levels in the striatum at 9 and 22-24 months of age (MGI Ref ID J:150206)
- behavior/neurological phenotype
- *normal* behavior/neurological phenotype
- unlike in human patients with early stage sporadic Parkinson's disease, acoustic startle reflexes are not impaired (MGI Ref ID J:150206)
- hypoactivity
- decrease in total distance covered, horizontal activity, movement time, stereotypy count and center distance in an open field test beginning at 16 months of age (MGI Ref ID J:150206)
- growth/size phenotype
- decreased body weight
- weigh up to 19% less than controls at 1 year of age (MGI Ref ID J:150206)
- cellular phenotype
- *normal* cellular phenotype
- unlike in Drosophila pink1 null mutants, no defects in mitochondrial fission are detected (MGI Ref ID J:150206)
- abnormal cellular respiration
- abnormal respiratory electron transport chain
- liver mitochondrial membrane potential shows a progressive age related reduction (MGI Ref ID J:150206)
- abnormal mitochondrial ATP synthesis coupled electron transport
- respiratory complex activity of purified liver mitochondria from 18 month old mice is significantly reduced compared to controls (MGI Ref ID J:150206)
- abnormal mitochondrial physiology
- assays indicate age-related impairment in liver mitochondrial import reactions (MGI Ref ID J:150206)
- abnormal respiratory electron transport chain
- liver mitochondrial membrane potential shows a progressive age related reduction (MGI Ref ID J:150206)
- abnormal mitochondrial ATP synthesis coupled electron transport
- respiratory complex activity of purified liver mitochondria from 18 month old mice is significantly reduced compared to controls (MGI Ref ID J:150206)
- endocrine/exocrine gland phenotype
- *normal* endocrine/exocrine gland phenotype
- unlike in human patients with early stage sporadic Parkinson's disease, increased sweating is not seen (MGI Ref ID J:150206)
- homeostasis/metabolism phenotype
- decreased dopamine level
- decreased dopamine levels in the striatum at 9 and 22-24 months of age (MGI Ref ID J:150206)
This mouse can be used to support research in many areas including:
Neurobiology Research
Ataxia (Movement) Defects
Behavioral and Learning Defects
high anxiety
Parkinson's Disease
Genes & Alleles
Gene & Allele Information provided by MGI
| Allele Symbol | Pink1tm1Aub | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Georg Auburger | ||
| Allele Type | Targeted (knock-in) | ||
| Mutation Made By | Georg Auburger, University Medical School | ||
| Strain of Origin | 129 | ||
| Promoter | Pink1, PTEN induced putative kinase 1, mouse, laboratory | ||
| Molecular Note | A G309D (g8343a) mutation was inserted in exon 4 and a floxed neo cassette in inverse orientation was inserted into intron 5 via homologous recombination. Northern blot and saturation RT-PCR of splice boundaries in brain and liver mRNA analysis confirmed the absence of full length transcript expression. Saturation RT-PCR also suggests the residual expression of low levels of a large mutant mRNA. [MGI Ref ID J:150206] | ||
Genotyping
Genotyping Information
Genotyping Protocols
Pink1tm1Aub alternate1,Separated MCA
Pink1tm1Aubalternate1, Separated PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
Selected Reference(s)
Gispert S; Ricciardi F; Kurz A; Azizov M; Hoepken HH; Becker D; Voos W; Leuner K; Muller WE; Kudin AP; Kunz WS; Zimmermann A; Roeper J; Wenzel D; Jendrach M; Garcia-Arencibia M; Fernandez-Ruiz J; Huber L; Rohrer H; Barrera M; Reichert AS; Rub U; Chen A; Nussbaum RL; Auburger G. 2009. Parkinson phenotype in aged PINK1-deficient mice is accompanied by progressive mitochondrial dysfunction in absence of neurodegeneration. PLoS One 4(6):e5777. [PubMed: 19492057] [MGI Ref ID J:150206]
Additional References
Pink1tm1Aub relatedDehorter N; Lozovaya N; Mdzomba BJ; Michel FJ; Lopez C; Tsintsadze V; Tsintsadze T; Klinkenberg M; Gispert S; Auburger G; Hammond C. 2012. Subthalamic lesion or levodopa treatment rescues giant GABAergic currents of PINK1-deficient striatum. J Neurosci 32(50):18047-53. [PubMed: 23238720] [MGI Ref ID J:192017]
Health & husbandry
Health & Colony Maintenance Information
Animal Health Reports
Room Number AX11
Colony Maintenance
Breeding & Husbandry When maintaining a live colony, homozygous mice may be bred together. Mating System Homozygote x Homozygote (Female x Male) 14-NOV-11 Diet Information LabDiet® 5K52/5K67
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $195.00 Female or Male Homozygous for Pink1tm1Aub
Price per Pair (US dollars $) Pair Genotype $390.00 Homozygous for Pink1tm1Aub x Homozygous for Pink1tm1Aub Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
| Pricing for International shipping destinations |
|
Live Mice
Price per mouse (US dollars $) Gender Genotypes Provided Individual Mouse $253.50 Female or Male Homozygous for Pink1tm1Aub
Price per Pair (US dollars $) Pair Genotype $507.00 Homozygous for Pink1tm1Aub x Homozygous for Pink1tm1Aub Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
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Standard Supply
Repository-Live.
Repository-Live represents an exclusive set of over 1500 unique mouse models across a vast array of research areas. Breeding colonies provide mice for both large and small orders and fluctuate in size depending on current demand for each strain. If a Repository strain is not immediately available, then within 2 to 3 business days, you will receive an estimated availability timeframe for your inquiry or order along with various delivery options. Repository strains typically are delivered at 4 to 8 weeks of age and will not exceed 12 weeks of age on the day of shipping. We will note and try to accommodate requests for specific ages of Repository strains but cannot guarantee provision of these strains at specific ages. However, if cohorts of mice (5 or more of one gender) are needed at a specific age range for experiments, please let us know.
Control Information
| Control | ||
|---|---|---|
| 101043 B6129SF1/J | (approximate) | |
| 101045 B6129SF2/J | (approximate) | |
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
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The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project.Ordering Information
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