JAX Mouse Strain Datasheet - 012441

STOCK Tg(tetO-LRRK2*G2019S)E3Cai/J

Stock No:: 012441

Transgenic

Cryo Recovery

Overview

These hemizygous transgenic mice carry a humanized leucine-rich repeat kinase 2 mutant gene, LRRK2*G2019S, regulated by a tetracycline operator (tetO). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of LRRK2*G2019S protein may be regulated with the tetracycline analog doxycycline (dox) in the double mutant offspring. These mice may be useful for studying the Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*G2019S expression.

Donating Investigator

Huaibin Cai, National Institutes of Health / National Institute on Aging (NIH/NIA)

Genetic overview

Genetic Background	Generation

Tg(tetO-LRRK2*G2019S)E3Cai

Allele Type
Transgenic (Humanized sequence, Inducible, Inserted expressed sequence)

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Research Applications

Neurobiology Research
Research Tools

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Base Price

Starting at:

$2,595.00 Domestic price Cryo Recovery

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Details

Detailed Description

Mice hemizygous for the human leucine-rich repeat kinase 2 mutant transgene, (LRRK2*G2019S), are viable and fertile. Expression of LRRK2*G2019S is regulated by a tetracycline operator (tetO); also called tetracycline-responsive element (TRE, TetRE) or tet-operator). When mated to a mutant strain expressing tetracycline-controlled transactivator protein (tTA), expression of LRRK2*G2019S protein may be regulated with tetracycline or its analog doxycycline (dox) in the double mutant offspring. LRRK2 protein, also known as Dardarin, contains multiple functional domains and may function as both an active GTPase and kinase. LRRK2 may regulate alpha-synuclein-mediated neuropathology through modulating the intracellular trafficking and accumulation of SNCA protein. The amino acid mutation in the kinase domain of LRRK2 may decrease proteasomal degradation of LRRK2. These mice may be useful for studying Parkinson's disease pathogenesis and neurodegeneration elicited by the dominant toxic effects of mutant LRRK2*G2019S expression.

When bred to a strain expressing tTA in forebrain neurons (see Stock No. 007004 for example), this mutant mouse strain may be useful in studies of neuronal morphegenesis.

Development

A transgenic vector was generated encoding the C-terminal hemagglutinin (HA)-tagged human LRRK2*G2019S mutant gene under control of a tetO promoter. The donating investigator reported that the construct was microinjected into C57BL/6J fertilized oocytes, and founder mice were bred to C57BL/6J mice to establish a colony (see SNP note below). Upon arrival at The Jackson Laboratory, mice were bred to C57BL/6J inbred mice (Stock No. 000664) for at least one generation to establish the colony.

A 32 SNP (single nucleotide polymorphism) panel analysis, with 27 markers covering all 19 chromosomes and the X chromosome, as well as 5 markers that distinguish between the C57BL/6J and C57BL/6N substrains, was performed on the rederived living colony at The Jackson Laboratory Repository. Five markers, on Ch 1, 2, 4, 5, and 11, were found to be segregating, suggesting mice sent to The Jackson Laboratory Repository were on a mixed genetic background.

Expression Data

Expressed Gene	LRRK2, leucine rich repeat kinase 2, human
Site of Expression

Control Suggestions

Noncarrier
000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Lin X; Parisiadou L; Gu XL; Wang L; Shim H; Sun L; Xie C; Long CX; Yang WJ; Ding J; Chen ZZ; Gallant PE; Tao-Cheng JH; Rudow G; Troncoso JC; Liu Z; Li Z; Cai H. 2009. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 64(6):807-27. PubMed: 20064389 MGI: J:156512
Parisiadou L; Xie C; Cho HJ; Lin X; Gu XL; Long CX; Lobbestael E; Baekelandt V; Taymans JM; Sun L; Cai H. 2009. Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis. J Neurosci 29(44):13971-80. PubMed: 19890007 MGI: J:154755
Wang L; Xie C; Greggio E; Parisiadou L; Shim H; Sun L; Chandran J; Lin X; Lai C; Yang WJ; Moore DJ; Dawson TM; Dawson VL; Chiosis G; Cookson MR; Cai H. 2008. The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J Neurosci 28(13):3384-91. PubMed: 18367605 MGI: J:133490

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Genetics

Tg(tetO-LRRK2*G2019S)E3Cai

Allele Symbol: Tg(tetO-LRRK2*G2019S)E3Cai

Allele Name	transgene insertion E3, Huaibin Cai
Allele Type	Transgenic (Humanized sequence, Inducible, Inserted expressed sequence)
Allele Synonym(s)	G2019S; LRRK2 G2019S; tetO-LRRK2 G2019S
Gene Symbol and Name	Tg(tetO-LRRK2*G2019S)E3Cai, transgene insertion E3, Huaibin Cai
Gene Synonym(s)	G2019S; LRRK2 G2019S; tetO-LRRK2 G2019S
Promoter	tetO, tet operator,
Expressed Gene	LRRK2, leucine rich repeat kinase 2, human
Strain of Origin	C57BL/6J
Chromosome	UN
Molecular Note	A transgenic vector was generated encoding the C-terminal hemagglutinin (HA)-tagged human LRRK2*G2019S mutant gene under control of a tetO promoter. The construct was microinjected into C57BL/6J fertilized oocytes, and three independent lines were generated. Founder mice were bred to C57BL/6J mice to establish the E3 line.
Mutations Made By	Huaibin Cai, National Institutes of Health / National Institute on Aging (NIH/NIA)

Disease/Phenotype

Disease Terms

Research Areas By Genotype

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

Neurobiology Research
- Neurodegeneration
- Parkinson's Disease
  - LRRK2 strains
- Tet Expression System
  - tTA/rtTA Responsive Strains
Research Tools
- Tet Expression Systems
  - tTA/rtTA Responsive Strains

Mammalian Phenotype Terms by Genotype

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

Genotype: Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0
involves: C57BL/6

growth/size/body region phenotype

decreased body weight
- starting at 1 year, mice appear to gain less body weight than non-transgenic and Tg(tetO-LRRK2*G2019S)E3Cai single mutant mice, but are not different from Tg(Camk2a-tTA)1Mmay animals

behavior/neurological phenotype

abnormal locomotor activation
- mice show significantly increased ambulatory activities starting at 12 months of age; at 12 months mice show a trend to increased rearing activities but this does not reach statistical significance

behavior/neurological phenotype
- mice show normal performance in the rotarod test

hyperactivity

nervous system phenotype

abnormal nervous system physiology
- brain homogenates moderately elevated levels of ubiquitinated proteins at 18 months compared to non-transgenic controls

abnormal neuron morphology
- at 1 month, the medial/trans-Golgi in neurons is significantly altered
- at 6 months fragmentation of the cis-Golgi apparatus is similar to that in LRRK2WT and A53T/LRRK2 neurons
- the Golgi complex is drastically altered in neurons at 1 month, appearing thinner and fragmented

nervous system phenotype
- no alpha-synuclein accumulation is observed in neurons at 20 months
- no increase in reactive astrocytosis or microglial activation are detected in the striatum or cortex at 20 months
- no significant changes in neuron counts are observed compared to non-transgenic controls at the frontal cortex or dorsal striatum in 6- or 20-month old mice

References

Lin X; Parisiadou L; Gu XL; Wang L; Shim H; Sun L; Xie C; Long CX; Yang WJ; Ding J; Chen ZZ; Gallant PE; Tao-Cheng JH; Rudow G; Troncoso JC; Liu Z; Li Z; Cai H. 2009. Leucine-rich repeat kinase 2 regulates the progression of neuropathology induced by Parkinson's-disease-related mutant alpha-synuclein. Neuron 64(6):807-27. PubMed: 20064389 MGI: J:156512
Parisiadou L; Xie C; Cho HJ; Lin X; Gu XL; Long CX; Lobbestael E; Baekelandt V; Taymans JM; Sun L; Cai H. 2009. Phosphorylation of ezrin/radixin/moesin proteins by LRRK2 promotes the rearrangement of actin cytoskeleton in neuronal morphogenesis. J Neurosci 29(44):13971-80. PubMed: 19890007 MGI: J:154755
Wang L; Xie C; Greggio E; Parisiadou L; Shim H; Sun L; Chandran J; Lin X; Lai C; Yang WJ; Moore DJ; Dawson TM; Dawson VL; Chiosis G; Cookson MR; Cai H. 2008. The chaperone activity of heat shock protein 90 is critical for maintaining the stability of leucine-rich repeat kinase 2. J Neurosci 28(13):3384-91. PubMed: 18367605 MGI: J:133490

Additional - Tg(tetO-LRRK2*G2019S)E3Cai related

Langston RG; Rudenko IN; Cookson MR. 2016. The function of orthologues of the human Parkinson's disease gene LRRK2 across species: implications for disease modelling in preclinical research. Biochem J 473(3):221-32. PubMed: 26811536 MGI: J:237645
Liu G; Sgobio C; Gu X; Sun L; Lin X; Yu J; Parisiadou L; Xie C; Sastry N; Ding J; Lohr KM; Miller GW; Mateo Y; Lovinger DM; Cai H. 2015. Selective expression of Parkinson's disease-related Leucine-rich repeat kinase 2 G2019S missense mutation in midbrain dopaminergic neurons impairs dopamine release and dopaminergic gene expression. Hum Mol Genet :. PubMed: 26123485 MGI: J:222392

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service	Genotype	Price
	Hemizygous or Non carrier for Tg(tetO-LRRK2*G2019S)E3Cai

Progeny testing is not required

The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided, their gender and genotype will vary. We will fulfill your order by providing at least two pair of mice, at least one animal of each pair carrying the mutation of interest. Please inquire if larger numbers of animals with specific genotype and genders are needed. Animals typically ship between 10 and 14 weeks from the date of your order. If a second cryorecovery is needed in order to provide the minimum number of animals, animals will ship within 25 weeks.

The genotypes of animals provided may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation, or that discussed in the strain description. Please inquire about possible genotypes which will be recovered for this specific strain. The Jackson Laboratory 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.

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Terms are granted by individual review and stated on the customer invoice(s) and account statement. These transactions are payable in U.S. currency within the granted terms. Payment for services, products, shipping containers, and shipping costs that are rendered are expected within the payment terms indicated on the invoice or stated by contract. Invoices and account balances in arrears of stated terms may result in The Jackson Laboratory pursuing collection activities including but not limited to outside agencies and court filings.

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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.

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Expression Data

Control Suggestions

Additional Information

Selected References

Tg(tetO-LRRK2*G2019S)E3Cai

Allele Symbol: Tg(tetO-LRRK2*G2019S)E3Cai

Disease Terms

Research Areas By Genotype

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

Mammalian Phenotype Terms by Genotype

Genotype: Tg(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0involves: C57BL/6

growth/size/body region phenotype

behavior/neurological phenotype

nervous system phenotype

References

Additional - Tg(tetO-LRRK2*G2019S)E3Cai related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Progeny testing is not required

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms of Use

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(Camk2a-tTA)1Mmay/0 Tg(tetO-LRRK2*G2019S)E3Cai/0
involves: C57BL/6