Strain Name:

B6;129-Lrrk2tm2.1Shn/J

Stock Number:

016209

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Availability:

Repository- Live

Use Restrictions Apply, see Terms of Use
LRRK2 KO1 mice have the promoter and exon 1 of the Lrrk2 gene deleted. These mice may be useful in studying the cellular function of LRRK2 during aging in the maintenance of protein homeostasis.

Description

Strain Information

Type Mutant Stock; Targeted Mutation;
Additional information on Genetically Engineered and Mutant Mice.
Visit our online Nomenclature tutorial.
Mating SystemHomozygote x Homozygote         (Female x Male)   10-APR-12
Specieslaboratory mouse
GenerationN?+F6 (11-DEC-13)
Generation Definitions
 
Donating Investigator Jie Shen,   Harvard Med Sch/Brigham Women's Hosp

Description
Mice homozygous for the LRRK2 KO1 mutation are viable and fertile, with the promoter and exon 1 of the Lrrk2 (leucine-rich repeat kinase 2) gene deleted. No mRNA or protein expression from the targeted allele is observed in brain tissues, however a truncated mRNA signal is observed in kidney tissue. Homozygous mice do not exhibit neurodegeneration or neuropathological changes in the brain. In the kidneys, a tissue where LRRK2 is normally expressed at ~6-fold greater levels than brain, homozygous loss of LRRK2 results in renal atrophy by 20 months of age. This is accompanied by significant (~60-fold) age-dependent accumulation of aggregated α-synuclein and ubiquitinated proteins in the kidney. Specifically, homozygous KO kidneys show widely distributed cytosolic α-synuclein-immunoreactive granular aggregates (some amy also contain phospho-Ser-129 α-synuclein) or inclusions in boxy cells of renal tubules in the cortical area by 20 months of age. Other kidney defects observed in homozygous mice include impaired ubiquitin-proteasome system(UPS)-mediated protein degradation, impaired autophagy-lysosomal pathway, increased apoptotic cell death, inflammatory response, and oxidative damage. These LRRK2 KO1 mice may be useful in studying the cellular function of LRRK2 during aging in the maintenance of protein homeostasis.

Development
A targeting vector was designed to replace the region encompassing the promoter and exon 1 of the Lrrk2 (leucine-rich repeat kinase 2) locus with a loxP-flanked PGK-neo cassette. This construct was electroporated into (C57BL/6 x 129)F1-derived MKV6.5 embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts. Chimeric mice were bred with B6/129 F1 mice to generate the mutant colony. Next, the mutant mice were bred with CaMKII-Cre transgenic mice on a B6 background. Offspring with the floxed PGK-neo cassette deleted in the germline were bred together (and the CaMKII-Cre transgene was selectively removed) for many generations. Upon arrival at The Jackson Laboratory Repository, mice were bred with B6129SF1/J hybrid mice (Stock No. 101043) for at least one generation to establish the colony.

Control Information

  Control
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls

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View Parkinson's Disease Models     (112 strains)

View Strains carrying other alleles of Lrrk2     (10 strains)

Additional Web Information

Visit the Parkinson's Disease Resource site for helpful information on Parkinson's and research resources.

Phenotype

Phenotype Information

View Related Disease (OMIM) Terms

Related Disease (OMIM) Terms provided by MGI
- Potential model based on gene homology relationships. Phenotypic similarity to the human disease has not been tested.
Parkinson Disease 8, Autosomal Dominant; PARK8   (LRRK2)
View Mammalian Phenotype Terms

Mammalian Phenotype Terms provided by MGI
      assigned by genotype

Lrrk2tm2.1Shn/Lrrk2tm2.1Shn

        involves: 129 * C57BL/6
  • renal/urinary system phenotype
  • abnormal kidney morphology
    • at 20 months, kidneys appear rough and granular, are smaller, weigh less, and are darker than in wild-type mice   (MGI Ref ID J:160542)
    • however, kidneys are normal at 10 weeks   (MGI Ref ID J:160542)
    • at 20 months, kidneys exhibit accumulation and aggregation of alpha-synuclein and ubiquitinated proteins compared with wild-type   (MGI Ref ID J:160542)
    • at 20 months, lipofuscin granules accumulate in the kidneys unlike in wild-type mice   (MGI Ref ID J:160542)
    • granular kidney
    • small kidney
      • decreased kidney weight
      • kidney atrophy
  • increased kidney apoptosis
    • at 20 months, mice exhibit increased apoptosis in the medulla, renal tubules, and glomeruli compared with wild-type mice   (MGI Ref ID J:160542)
    • at 20 months, kidneys exhibit impaired autophagy-lysosomal pathways compared with wild-type kidneys   (MGI Ref ID J:160542)
    • increased renal glomerulus apoptosis
    • increased renal tubule apoptosis
  • kidney inflammation
  • cellular phenotype
  • abnormal autophagy
    • at 20 months, kidneys exhibit impaired autophagy-lysosomal pathways compared with wild-type kidneys   (MGI Ref ID J:160542)
  • increased kidney apoptosis
    • at 20 months, mice exhibit increased apoptosis in the medulla, renal tubules, and glomeruli compared with wild-type mice   (MGI Ref ID J:160542)
    • at 20 months, kidneys exhibit impaired autophagy-lysosomal pathways compared with wild-type kidneys   (MGI Ref ID J:160542)
    • increased renal glomerulus apoptosis
    • increased renal tubule apoptosis
  • pigmentation phenotype
  • lipofuscinosis
    • at 20 months, lipofuscin granules accumulate in the kidneys unlike in wild-type mice   (MGI Ref ID J:160542)
  • nervous system phenotype
  • *normal* nervous system phenotype
    • mice exhibit normal dopaminergic neurons and dopamine turnover   (MGI Ref ID J:160542)
  • immune system phenotype
  • kidney inflammation
View Research Applications

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

Developmental Biology Research
Internal/Organ Defects
      kidney

Endocrine Deficiency Research
Kidney Defects

Internal/Organ Research
Kidney Defects
      lysosomal enzyme abnormalities

Neurobiology Research
Parkinson's Disease
      LRRK2 strains

Genes & Alleles

Gene & Allele Information provided by MGI

 
Allele Symbol Lrrk2tm2.1Shn
Allele Name targeted mutation 2.1, Jie Shen
Allele Type Targeted (knock-out)
Common Name(s) Lrrk2KO1;
Mutation Made By Jie Shen,   Harvard Med Sch/Brigham Women's Hosp
Strain of Origin(C57BL/6 x 129)F1
Gene Symbol and Name Lrrk2, leucine-rich repeat kinase 2
Chromosome 15
Gene Common Name(s) 4921513O20Rik; 9330188B09Rik; AURA17; AW561911; D630001M17Rik; DARDARIN; Gm927; LOC381026; PARK8; RIKEN cDNA 4921513O20 gene; RIKEN cDNA 9330188B09 gene; RIKEN cDNA D630001M17 gene; RIPK7; ROCO2; cDNA sequence, clone 3-75; cI-46; gene model 927, (NCBI);
Molecular Note The promoter region and exon 1 were replaced with a floxed neo cassette. Cre mediated recombination removed the neo cassette. The absence of protein expression was confirmed by western blot analysis on brain extracts. [MGI Ref ID J:160542]

Genotyping

Genotyping Information

Genotyping Protocols

Lrrk2tm2.1Shn, Standard PCR


Helpful Links

Genotyping resources and troubleshooting

References

References provided by MGI

Selected Reference(s)

Tong Y; Yamaguchi H; Giaime E; Boyle S; Kopan R; Kelleher RJ 3rd; Shen J. 2010. Loss of leucine-rich repeat kinase 2 causes impairment of protein degradation pathways, accumulation of {alpha}-synuclein, and apoptotic cell death in aged mice. Proc Natl Acad Sci U S A 107(21):9879-84. [PubMed: 20457918]  [MGI Ref ID J:160542]

Health & husbandry

Health & Colony Maintenance Information

Animal Health Reports

Room Number           AX10

Colony Maintenance

Breeding & HusbandryWhen maintaining a live colony, homozygous mice may be bred together.
Mating SystemHomozygote x Homozygote         (Female x Male)   10-APR-12
Diet Information LabDiet® 5K52/5K67

Pricing and Purchasing

Pricing, Supply Level & Notes, Controls


Pricing for USA, Canada and Mexico shipping destinations View International Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $232.00Female or MaleHomozygous for Lrrk2tm2.1Shn  
Price per Pair (US dollars $)Pair Genotype
$464.00Homozygous for Lrrk2tm2.1Shn x Homozygous for Lrrk2tm2.1Shn  

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 View USA Canada and Mexico Pricing

Live Mice

Price per mouse (US dollars $)GenderGenotypes Provided
Individual Mouse $301.60Female or MaleHomozygous for Lrrk2tm2.1Shn  
Price per Pair (US dollars $)Pair Genotype
$603.20Homozygous for Lrrk2tm2.1Shn x Homozygous for Lrrk2tm2.1Shn  

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.

View USA Canada and Mexico Pricing View International Pricing

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
   000664 C57BL/6J (approximate)
 
  Considerations for Choosing Controls
  Control Pricing Information for Genetically Engineered Mutant Strains.
 

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