Description

Strain Information

Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered Mutant Mice. Species laboratory mouse Generation N17p (11-DEC-05)   Donating Investigator Bruce Aronow,   Cincinnati Children's Hospital Med Cntr

Description
Mice that are homozygous for the targeted mutation are viable, fertile, normal in size, and do not display any behavioral abnormalities. No protein is detected in serum, liver, or brain and in situ hybridization shows no mRNA in heart. This mutant has been studied for different functions on different backgrounds. On the Swiss Black outbred background, aging homozygous mutant mice develop a progressive glomerulopathy characterized by deposition of tubulo-fibrillary immune complexes devoid of inflammation or necrosis. On the FVB/N background, homozygous null mice with chemically induced autoimmune myocarditis show severe and diffuse lesions with postinflammatory functional impairment. Induced skin carcinogenesis is more severe than wildtype. On the C57BL/6 background, homozygotes given a hypoxia-ischemia brain injury (modeling cerebral palsy) had 50% less brain injury compared to wild type. Conversely, mutants have less neuroprotective properties after permanent focal cerebral ischemia, a mouse model of human stroke. Mutant mice have altered heat-induced apoptosis in the testis. This mutant confers less fibrillar amyloid-beta damage and less neuritic dystrophy when bred with Alzheimer's disease model mice compared to control. This mutant mouse strain contains a targeted mutation of a widely expressed circulating glycoprotein associated with Alzheimer's disease, cerebral palsy, stroke, apoptosis, autoimmune myocarditis, kidney disease, and skin carcinogenesis.

Development
A targeting vector was constructed in which exon 1 and 2 of the endogenous gene were replaced with a mouse phosphoglycerol kinase promoter driven hypoxanthine phosphoribosyl-transferase gene. The construct was electroporated into 129S2/SvPas-derived D3 embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts which were then implanted into pseudopregnant (C3H/HeN x C57BL/6J)F1 females. The resulting chimeric males were backcrossed for germ-line transmission to CF1 females. Heterozygotes were backcrossed to the Black Swiss outbred strain for one generation and then to C57BL/6J for more than 7 generations.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Additional Web Information

Congenic Nomenclature
Genetic Quality Control Annual Report
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.

Phenotype

Phenotype Information

View Mammalian Phenotype Terms

Mammalian Phenotype Terms

      assigned by genotype

The following phenotype information may relate to a genetic background differing from this JAX^® Mice strain.

Clu^tm1Jakh/Clu^tm1Jakh

        involves: Black Swiss * FVB/N

• cardiovascular system phenotype
• abnormal heart morphology (MGI Ref ID J:65660)
  • after immunization with cardiac myosin, mutant hearts become pale and enlarged, mutants exhibit 3-fold greater heart tissue injury than wild-type
• abnormal cardiac muscle morphology (MGI Ref ID J:65660)
  • 21 days after myocarditis initiation, mice show significant cardiac tissue injury than wild-type mice
• abnormal myocardial fiber morphology (MGI Ref ID J:65660)
  • after immunization, myocyte necrosis is observed in some animals
• decreased myocardial fiber number (MGI Ref ID J:65660)
  • 7 weeks following myocarditis, widespread loss of myocardial fibers is found in mutant hearts, whereas none is seen in wild-type controls
• abnormal heart ventricle morphology (MGI Ref ID J:65660)
  • ventricular damage in females is 6-fold greater than in wild-type females; males do not show as severe cardiac damage
• decreased cardiac muscle contractility (MGI Ref ID J:65660)
  • postmyocarditis heart function is impaired with decreased shortening fraction measured in mutants;
• heart inflammation (MGI Ref ID J:65660)
  • severe, diffuse inflammation with large inflammatory aggregates occurs after immunization with cardiac myosin
• myocarditis (MGI Ref ID J:65660)
  • severe myocarditis after immunization with cardiac myosin, more severe than in wild-type
• muscle phenotype
• abnormal cardiac muscle morphology (MGI Ref ID J:65660)
  • 21 days after myocarditis initiation, mice show significant cardiac tissue injury than wild-type mice
• abnormal myocardial fiber morphology (MGI Ref ID J:65660)
  • after immunization, myocyte necrosis is observed in some animals
• decreased myocardial fiber number (MGI Ref ID J:65660)
  • 7 weeks following myocarditis, widespread loss of myocardial fibers is found in mutant hearts, whereas none is seen in wild-type controls
• decreased cardiac muscle contractility (MGI Ref ID J:65660)
  • postmyocarditis heart function is impaired with decreased shortening fraction measured in mutants;
• immune system phenotype
• heart inflammation (MGI Ref ID J:65660)
  • severe, diffuse inflammation with large inflammatory aggregates occurs after immunization with cardiac myosin
• myocarditis (MGI Ref ID J:65660)
  • severe myocarditis after immunization with cardiac myosin, more severe than in wild-type
• homeostasis/metabolism phenotype
• edema (MGI Ref ID J:65660)
  • immunized mice show cardiac edema

Clu^tm1Jakh/Clu^tm1Jakh

        involves: 129S2/SvPas

• nervous system phenotype
• *normal* nervous system phenotype (MGI Ref ID J:58019)
  • astrocytes secrete a normal composition of lipid particles

View Research Applications

Research Applications

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

Cardiovascular Research
Ischemia studies

Developmental Biology Research
Internal/Organ Defects (brain)

Neurobiology Research
Alzheimer's Disease

Research Tools
Apoptosis Research

Genes & Alleles

Gene & Allele Information

Allele Symbol		Clutm1Jakh
Allele Name		targeted mutation 1, Judith A K Harmony
Allele Type		Targeted (knock-out)
Mutation Made By		Bruce Aronow,   Cincinnati Children's Hospital Med Cntr
Strain of Origin		129S2/SvPas
ES Cell Line Name		D3
ES Cell Line Strain		129S2/SvPas
Gene Symbol and Name		Clu, clusterin
Chromosome		14
Gene Common Name(s)		AAG4; AI893575; APOJ; Apolipoprotein J; CLI; Cli; D14Ucla3; DNA segment, Chr 14, University of California at Los Angeles 3; KUB1; MGC24903; RATTRPM2B; SGP-2; SGP2; SP-40; Sugp-2; TRPM-2; TRPM2; TRPM2B; Trpmb; complement lysis inhibitor; expressed sequence AI893575; sulfated glycoprotein 2; testosterone repressed prostate message;
Molecular Note		The insertion of an HPRT cassette deleted exons 1 and 2. Normal transcript was undetectable in homozygous mutant tissue. Western blot analysis of plasma and liver extracts showed an absence of protein in homozygous mutant mice. [MGI Ref ID J:2892] [MGI Ref ID J:65660] [MGI Ref ID J:67960]

Genotyping

Genotyping Information

Genotyping Protocols

Clu^tm1Jakh, STD PCR, vers. 1

Helpful Links

Optimizing PCR Protocols

References

References

Selected Reference(s)

McLaughlin L; Zhu G; Mistry M; Ley-Ebert C; Stuart WD; Florio CJ; Groen PA; Witt SA; Kimball TR; Witte DP; Harmony JA; Aronow BJ. 2000. Apolipoprotein J/clusterin limits the severity of murine autoimmune myocarditis J Clin Invest 106(9):1105-13. [PubMed: 11067863]  [MGI Ref ID J:65660]

Additional References

Clu^tm1Jakh related

Bailey RW; Aronow B; Harmony JA; Griswold MD. 2002. Heat Shock-Initiated Apoptosis Is Accelerated and Removal of Damaged Cells Is Delayed in the Testis of Clusterin/ApoJ Knock-Out Mice. Biol Reprod 66(4):1042-53. [PubMed: 11906924]  [MGI Ref ID J:75670]

Charnay Y; Imhof A; Vallet PG; Hakkoum D; Lathuiliere A; Poku N; Aronow B; Kovari E; Bouras C; Giannakopoulos P. 2008. Clusterin expression during fetal and postnatal CNS development in mouse. Neuroscience 155(3):714-24. [PubMed: 18620027]  [MGI Ref ID J:140877]

DeMattos RB; Cirrito JR; Parsadanian M; May PC; O'Dell MA; Taylor JW; Harmony JA; Aronow BJ; Bales KR; Paul SM; Holtzman DM. 2004. ApoE and clusterin cooperatively suppress Abeta levels and deposition: evidence that ApoE regulates extracellular Abeta metabolism in vivo. Neuron 41(2):193-202. [PubMed: 14741101]  [MGI Ref ID J:107702]

DeMattos RB; O'dell MA; Parsadanian M; Taylor JW; Harmony JA; Bales KR; Paul SM; Aronow BJ; Holtzman DM. 2002. Clusterin promotes amyloid plaque formation and is critical for neuritic toxicity in a mouse model of Alzheimer's disease. Proc Natl Acad Sci U S A 99(16):10843-8. [PubMed: 12145324]  [MGI Ref ID J:78357]

Fagan AM; Holtzman DM; Munson G; Mathur T; Schneider D; Chang LK; Getz GS; Reardon CA; Lukens J; Shah JA; LaDu MJ. 1999. Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-), and human apoE transgenic mice. J Biol Chem 274(42):30001-7. [PubMed: 10514484]  [MGI Ref ID J:58019]

Han BH; DeMattos RB; Dugan LL; Kim-Han JS; Brendza RP; Fryer JD; Kierson M; Cirrito J; Quick K; Harmony JA; Aronow BJ; Holtzman DM. 2001. Clusterin contributes to caspase-3-independent brain injury following neonatal hypoxia-ischemia. Nat Med 7(3):338-43. [PubMed: 11231633]  [MGI Ref ID J:67960]

Hughes AT; Guilding C; Lennox L; Samuels RE; McMahon DG; Piggins HD. 2008. Live imaging of altered period1 expression in the suprachiasmatic nuclei of Vipr2-/- mice. J Neurochem 106(4):1646-57. [PubMed: 18554318]  [MGI Ref ID J:138727]

Imhof A; Charnay Y; Vallet PG; Aronow B; Kovari E; French LE; Bouras C; Giannakopoulos P. 2006. Sustained astrocytic clusterin expression improves remodeling after brain ischemia. Neurobiol Dis 22(2):274-83. [PubMed: 16473512]  [MGI Ref ID J:111243]

Kempster S; Collins ME; Aronow BJ; Simmons M; Green RB; Edington N. 2004. Clusterin shortens the incubation and alters the histopathology of bovine spongiform encephalopathy in mice. Neuroreport 15(11):1735-8. [PubMed: 15257138]  [MGI Ref ID J:103644]

Rosenberg ME; Girton R; Finkel D; Chmielewski D; Barrie A rd; Witte DP; Zhu G; Bissler JJ; Harmony JA; Aronow BJ. 2002. Apolipoprotein J/clusterin prevents a progressive glomerulopathy of aging. Mol Cell Biol 22(6):1893-902. [PubMed: 11865066]  [MGI Ref ID J:74983]

Savkovic V; Gantzer H; Reiser U; Selig L; Gaiser S; Sack U; Kloppel G; Mossner J; Keim V; Horn F; Bodeker H. 2007. Clusterin is protective in pancreatitis through anti-apoptotic and anti-inflammatory properties. Biochem Biophys Res Commun 356(2):431-7. [PubMed: 17359935]  [MGI Ref ID J:121479]

Shull MM; Ormsby I; Kier AB; Pawlowski S; Diebold RJ; Yin M; Allen R; Sidman C; Proetzel G; Calvin D; Annunziata N; Doetschman T. 1992. Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359(6397):693-9. [PubMed: 1436033]  [MGI Ref ID J:2892]

Tesseur I; Wyss-Coray T. 2006. A role for TGF-beta signaling in neurodegeneration: evidence from genetically engineered models. Curr Alzheimer Res 3(5):505-13. [PubMed: 17168649]  [MGI Ref ID J:125213]

Thomas-Tikhonenko A; Viard-Leveugle I; Dews M; Wehrli P; Sevignani C; Yu D; Ricci S; el-Deiry W; Aronow B; Kaya G; Saurat JH; French LE. 2004. Myc-transformed epithelial cells down-regulate clusterin, which inhibits their growth in vitro and carcinogenesis in vivo. Cancer Res 64(9):3126-36. [PubMed: 15126350]  [MGI Ref ID J:89749]

Wehrli P; Charnay Y; Vallet P; Zhu G; Harmony J; Aronow B; Tschopp J; Bouras C; Viard-Leveugle I; French LE; Giannakopoulos P. 2001. Inhibition of post-ischemic brain injury by clusterin overexpression. Nat Med 7(9):977-9. [PubMed: 11533682]  [MGI Ref ID J:99683]

Wicher GK; Aldskogius H. 2005. Adult motor neurons show increased susceptibility to axotomy-induced death in mice lacking clusterin. Eur J Neurosci 21(7):2024-8. [PubMed: 15869496]  [MGI Ref ID J:101072]

Health & husbandry

Health & Colony Maintenance Information

Colony Maintenance

Breeding & Husbandry	Homozygotes are viable and fertile. The donating investigator indicates that these mice can be maintained on a high fat diet to increase viability and fecundity, but it is not required.

Purchasing information

Pricing, Supply Level & Notes, Controls, General Terms & Conditions

Pricing

Supply Details

Standard Supply

Repository-Cryopreserved. Must Be Recovered. Please refer to pricing and supply notes for further information.

Supply Notes

Cryorecovery - Standard. The recovery process begins when a signed agreement form is returned to the Customer Service Department after order placement. Although results vary by strain, at least two males and two females (two pairs) will be provided, typically within 15 weeks of our receipt of the signed agreement form. If the first recovery attempt is unsuccessful or only one pair is recovered, a second recovery will be done, extending the delivery time to approximately 25 weeks. At least one member of each pair will be of known genotype and will carry the mutation if it is a mutant strain. Please note that pairs may not reflect the mating scheme utilized by The Jackson Laboratory prior to cryopreservation of the strain. Mating schemes are sometimes modified for successful cryopreservation. Price represents a repository maintenance fee, which includes the cost of recovery of the strain from the cryopreservation resource and the periodic replacement of the frozen embryos used for recovery. Cryorecovery to establish a Dedicated Supply for greater quantities of mice. One to two pairs will be recovered to establish a Dedicated Supply of mice. Price by quotation. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 or 1-207-288-5845. This strain is included in the Induced Mutant Resource Colony collection.

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls
USA, Canada and Mexico - Control Pricing Information for Genetically Engineered Mutant Strains.
International - Control Pricing Information for Genetically Engineered Mutant Strains.

General Terms and Conditions

See Terms of Use

The Jackson Laboratory's Genotype Promise

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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Ordering and Purchasing Information

      Purchasing Information
      JAX^® Mice Orders
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Contact Information
Orders & Technical Support
Tel: 800.422.6423 or 207.288.5845
Fax: 207.288.6150
Technical Support Email Form

Terms of Use

Terms of Use

General Terms and Conditions

For Licensing and Use Restrictions view the link(s) below:
- Use of MICE by companies or for-profit entities requires a license prior to shipping.

Contact information

General inquiries

Contracts Administration

phone:	207-288-6470
fax:	207-288-6655

JAX^® Mice & Services Conditions of Use

“Each recipient institution, including its employees and other researchers under its control (RECIPIENT), of mice or services using mice from The Jackson Laboratory (TJL) agrees that such mice, descendants of those mice derived by inbreeding or crossbreeding, including unmodified derivatives of those mice or their descendants (“MICE”) shall not be: (i) used for any purpose other than the internal research of the RECIPIENT, (ii) sold or otherwise provided to any third party for any use, or (iii) provided to any agent or other third party to provide breeding or other services with respect to MICE. Acceptance of MICE from TJL shall be deemed agreement by RECIPIENT to these conditions, and departure from these conditions requires The Jackson Laboratory’s prior written authorization.”

In case of dissatisfaction for a valid reason and claimed in writing by a purchaser within ninety (90) days of receipt of MICE, products or services, The Jackson Laboratory will, at its option, provide credit or replacement for the MICE or product received or the services provided.

No Liability

In no event shall The Jackson Laboratory, its trustees, directors, officers, employees, and affiliates be liable for any causes of action or damages, including any direct, indirect, special, or consequential damages, arising out of the provision of MICE, products or services, including economic damage or injury to property and lost profits, and including any damage arising from acts or negligence on the part of The Jackson Laboratory, its agents or employees. In purchasing or receiving MICE, products or services from The Jackson Laboratory, purchaser or recipient, or any party claiming by or through them, expressly releases and discharges The Jackson Laboratory from all such causes of action or damages, and further agrees to defend and indemnify The Jackson Laboratory from any costs or damages arising out of any third party claims.

MICE and biological materials are to be used in a safe manner and in accordance with all applicable governmental rules and regulations.

The foregoing represents the General Terms and Conditions applicable to The Jackson Laboratory’s MICE, products and services. In addition, special terms and conditions of sale of certain MICE, products and services may be set forth separately in The Jackson Laboratory web pages, catalogs, price lists, contracts, and/or other documents, and these special terms and conditions shall also govern the sale of these MICE, products and services by The Jackson Laboratory, and by its licensees and distributors.

Acceptance of delivery of MICE, products or services shall be deemed agreement to these terms and conditions. No purchase order or other document transmitted by purchaser or recipient that may modify the terms and conditions hereof, shall be in any way binding on The Jackson Laboratory, and instead the terms and conditions set forth herein, including any special terms and conditions set forth separately, shall govern the sale of MICE, products services by The Jackson Laboratory.