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Genes & Alleles

Clu;   Clutm1Jakh;

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Product Information

Strain Details

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

Strain 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.

Strain 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.

Mammalian Phenotype Terms 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 (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 Clutm1Jakh/Clutm1Jakh         involves: 129S2/SvPas nervous system phenotype *normal* nervous system phenotype (MGI Ref ID J:58019) astrocytes secrete a normal composition of lipid particles

Gene & Allele Details

Allele Symbol		Clutm1Jakh
Allele Name		targeted mutation 1, Judith A K Harmony
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]

Control Information

	Control
	Wild-type from the colony
Considerations for Choosing Controls

Genotyping Protocols

Clu^tm1Jakh

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.

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.

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

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

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Price and Supply Information

Strain Name:	B6.Cg-Clutm1Jakh/J
Stock Number:	005642

Price Details

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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; Email: jaxservices@jax.org. This strain is included in the Induced Mutant Resource Colony collection. Genomic DNA is available for this strain from the Mouse DNA Resource.
Licensing	See General Terms and Conditions below for Licensing and Use Restrictions
Control Information	View Control Information in Strain Details.

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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.

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