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- Description
- Disease & phenotype
- Genes & alleles
- Genotyping
- Health & care
- References
- Pricing & purchasing
- Terms of use
Description
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Strain Information
Type Congenic; Mutant Strain; Targeted Mutation; Additional information on Genetically Engineered and Mutant Mice. Visit our online Nomenclature tutorial. Additional information on Congenic nomenclature. Species laboratory mouse Generation N17p (11-DEC-05)
Generation DefinitionsDonating 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 | ||
Related Strains
Alzheimer's Disease Models
View Alzheimer's Disease Models (107 strains)
Additional Web Information
Visit the Alzheimer's Disease Mouse Model Resource site for helpful information on Alzheimer's Disease and research resources.
Phenotype
Phenotype Information
assigned by genotype
The following phenotype information may relate to a genetic background differing from this JAX® Mice strain.
Clutm1Jakh/Clutm1Jakh
involves: Black Swiss * FVB/N
- cardiovascular system phenotype
- abnormal heart morphology
- after immunization with cardiac myosin, mutant hearts become pale and enlarged, mutants exhibit 3-fold greater heart tissue injury than wild-type (MGI Ref ID J:65660)
- abnormal heart ventricle morphology
- ventricular damage in females is 6-fold greater than in wild-type females; males do not show as severe cardiac damage (MGI Ref ID J:65660)
- abnormal myocardium layer morphology
- 21 days after myocarditis initiation, mice show significant cardiac tissue injury than wild-type mice (MGI Ref ID J:65660)
- abnormal myocardial fiber morphology
- after immunization, myocyte necrosis is observed in some animals (MGI Ref ID J:65660)
- decreased myocardial fiber number
- 7 weeks following myocarditis, widespread loss of myocardial fibers is found in mutant hearts, whereas none is seen in wild-type controls (MGI Ref ID J:65660)
- decreased cardiac muscle contractility
- postmyocarditis heart function is impaired with decreased shortening fraction measured in mutants; (MGI Ref ID J:65660)
- heart inflammation
- severe, diffuse inflammation with large inflammatory aggregates occurs after immunization with cardiac myosin (MGI Ref ID J:65660)
- myocarditis
- severe myocarditis after immunization with cardiac myosin, more severe than in wild-type (MGI Ref ID J:65660)
- muscle phenotype
- abnormal myocardial fiber morphology
- after immunization, myocyte necrosis is observed in some animals (MGI Ref ID J:65660)
- decreased myocardial fiber number
- 7 weeks following myocarditis, widespread loss of myocardial fibers is found in mutant hearts, whereas none is seen in wild-type controls (MGI Ref ID J:65660)
- decreased cardiac muscle contractility
- postmyocarditis heart function is impaired with decreased shortening fraction measured in mutants; (MGI Ref ID J:65660)
- immune system phenotype
- heart inflammation
- severe, diffuse inflammation with large inflammatory aggregates occurs after immunization with cardiac myosin (MGI Ref ID J:65660)
- myocarditis
- severe myocarditis after immunization with cardiac myosin, more severe than in wild-type (MGI Ref ID J:65660)
- homeostasis/metabolism phenotype
- edema
- immunized mice show cardiac edema (MGI Ref ID J:65660)
Clutm1Jakh/Clutm1Jakh
involves: 129S2/SvPas
- nervous system phenotype
- *normal* nervous system phenotype
- astrocytes secrete a normal composition of lipid particles (MGI Ref ID J:58019)
Clutm1Jakh/Clutm1Jakh
involves: 129S2/SvPas * Black Swiss
- renal/urinary system phenotype
- *normal* renal/urinary system phenotype
- abnormal glomerular capillary morphology
- collapse of capillary lumens at 21 months of age (MGI Ref ID J:74983)
- abnormal glomerular mesangium morphology
- up to 75% of glomeruli exhibit moderate to severe mesangial lesions at 21 months of age (MGI Ref ID J:74983)
- abnormal mesangial matrix morphology
- electron-dense tubulo-fibrillar structures arranged in parallel arrays are detected in the mesangial matrix at 21 months, consistent with immune complex deposits (MGI Ref ID J:74983)
- more electron-dense deposits found in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet (MGI Ref ID J:74983)
- mesangial cell hyperplasia
- mesangial hypercellularity noted in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet (MGI Ref ID J:74983)
- cortical renal glomerulopathies
- at 21 months of age, mice display progressive mesangial expansion, collapse of capillary lumens, and deposition of collagen and immune complexes, unlike wild-type and heterozygous controls (MGI Ref ID J:74983)
- immune complexes of IgG, IgM, IgA, and in some cases C1q, C3, and C9 are detected in the mesangium at 21 months of age (MGI Ref ID J:74983)
- immune complexes of IgG, IgM and IgA are noted as early as 4 weeks of age (MGI Ref ID J:74983)
- increased deposition of C1q and C3 in 6-mo-old mice that have undergone unilateral nephrectomy at 3 months and are then fed a high-protein diet (MGI Ref ID J:74983)
- hematuria
- an occasional mutant develops hematuria (MGI Ref ID J:74983)
- renal glomerulus fibrosis
- accumulation of collagen deposits in the glomeruli (MGI Ref ID J:74983)
- homeostasis/metabolism phenotype
- *normal* homeostasis/metabolism phenotype
- mice display no signs of proteinuria or any alterations in serum and urine proteins relative to controls (MGI Ref ID J:74983)
- hematuria
- an occasional mutant develops hematuria (MGI Ref ID J:74983)
- cardiovascular system phenotype
- abnormal glomerular capillary morphology
- collapse of capillary lumens at 21 months of age (MGI Ref ID J:74983)
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 provided by MGI
| Allele Symbol | Clutm1Jakh | ||
|---|---|---|---|
| Allele Name | targeted mutation 1, Judith A K Harmony | ||
| Allele Type | Targeted (knock-out) | ||
| Common Name(s) | CLU-; | ||
| 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) | AI893575; APOJ; Apolipoprotein J; CLI; Cli; D14Ucla3; DAG; DNA segment, Chr 14, University of California at Los Angeles 3; RATTRPM2B; SGP-2; SGP2; SP-40; SP40; Sugp-2; TRPM-2; TRPM2B; Trpm2; Trpmb; complement lysis inhibitor; expressed sequence AI893575; sulfated glycoprotein 2; testosterone repressed prostate message-2; | ||
| Molecular Note | An HPRT cassette replaced 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
Clutm1Jakh, Fast MCA
Clutm1Jakh, Standard PCR
Helpful Links
Genotyping resources and troubleshooting
References
References provided by MGI
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
Clutm1Jakh relatedBailey 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]
Bettuzzi S; Davalli P; Davoli S; Chayka O; Rizzi F; Belloni L; Pellacani D; Fregni G; Astancolle S; Fassan M; Corti A; Baffa R; Sala A. 2009. Genetic inactivation of ApoJ/clusterin: effects on prostate tumourigenesis and metastatic spread. Oncogene 28(49):4344-52. [PubMed: 19784068] [MGI Ref ID J:157040]
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]
Chayka O; Corvetta D; Dews M; Caccamo AE; Piotrowska I; Santilli G; Gibson S; Sebire NJ; Himoudi N; Hogarty MD; Anderson J; Bettuzzi S; Thomas-Tikhonenko A; Sala A. 2009. Clusterin, a haploinsufficient tumor suppressor gene in neuroblastomas. J Natl Cancer Inst 101(9):663-77. [PubMed: 19401549] [MGI Ref ID J:148260]
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]
Lee S; Hong SW; Min BH; Shim YJ; Lee KU; Lee IK; Bendayan M; Aronow BJ; Park IS. 2011. Essential role of clusterin in pancreas regeneration. Dev Dyn 240(3):605-15. [PubMed: 21290478] [MGI Ref ID J:168536]
Monks DC; Morrow BE. 2012. Identification of putative retinoic acid target genes downstream of mesenchymal Tbx1 during inner ear development. Dev Dyn 241(3):563-73. [PubMed: 22275070] [MGI Ref ID J:181273]
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]
Zhou W; Guan Q; Kwan CC; Chen H; Gleave ME; Nguan CY; Du C. 2010. Loss of clusterin expression worsens renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 298(3):F568-78. [PubMed: 20007348] [MGI Ref ID J:157467]
Health & husbandry
The genotypes of the animals provided may not reflect those discussed in the strain description or the mating scheme utilized by The Jackson Laboratory prior to cryopreservation. Please inquire for possible genotypes for this specific strain.
Health & Colony Maintenance Information
Animal Health Reports
Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200.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.
Pricing and Purchasing
Pricing, Supply Level & Notes, Controls
| Pricing for USA, Canada and Mexico shipping destinations |
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Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $2450.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
| Pricing for International shipping destinations |
|
Cryopreserved
Cryopreserved Mice - Ready for Recovery
Animals Provided
Price (US dollars $) Cryorecovery* $3185.00 At least two mice that carry the mutation (if it is a mutant strain) will be provided. Their genotypes may not reflect those discussed in the strain description. Please inquire for possible genotypes and see additional details below.
Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
Supply Notes
Cryorecovery - Standard.
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 11 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. IMPORTANT NOTE: 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. For more information on Dedicated Supply, please contact JAX® Services, Tel: 1-800-422-6423 (from U.S.A., Canada or Puerto Rico only) or 1-207-288-5845 (from any location).
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Standard Supply
Cryopreserved. Ready for recovery. Please refer to pricing and supply notes on the strain data sheet for further information.
General Supply Notes
- Genomic DNA is available for this strain from the Mouse DNA Resource.
Control Information
| Control | ||
|---|---|---|
| Wild-type from the colony | ||
| Considerations for Choosing Controls | ||
| Control Pricing Information for Genetically Engineered Mutant Strains. | ||
Payment Terms and Conditions
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'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.Ordering Information
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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
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JAX® Mice, Products & Services Conditions of Use
"MICE" means mouse strains, their progeny derived by inbreeding or crossbreeding, unmodified derivatives from mouse strains or their progeny supplied by The Jackson Laboratory ("JACKSON"). "PRODUCTS" means biological materials supplied by JACKSON, and their derivatives. "RECIPIENT" means each recipient of MICE, PRODUCTS, or services provided by JACKSON including each institution, its employees and other researchers under its control. MICE or PRODUCTS shall not be: (i) used for any purpose other than the internal research, (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. Acceptance of MICE or PRODUCTS from JACKSON shall be deemed as agreement by RECIPIENT to these conditions, and departure from these conditions requires JACKSON's prior written authorization.No Warranty
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