These Clu (also referred to as apoJ/clusterinJ) mice contain a targeted mutation of a glycoprotein associated with Alzheimer's disease and exhibit less neuroprotective properties after permanent focal cerebral ischemia.
Bruce Aronow, Cincinnati Children's Hospital Med Cntr
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.
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.
|Allele Name||targeted mutation 1, Judith A K Harmony|
|Allele Type||Targeted (Null/Knockout)|
|Gene Symbol and Name||Clu, clusterin|
|Gene Synonym(s)||AAG4; AI893575; APO-J; APOJ; ApoJ; Apolipoprotein J; CLI; CLU1; CLU2; Cli; Cli; D14Ucla3; D14Ucla3; DAG; DNA segment, Chr 14, University of California at Los Angeles 3; KUB1; NA1/NA2; RATTRPM2B; SGP-2; SGP2; SP-40; SP40; Sgp-2; Sgp2; Sugp-2; Sugp-2; TRPM-2; TRPM2; TRPM2B; Trpm2; Trpmb; complement lysis inhibitor; complement lysis inhibitor; expressed sequence AI893575; sulfated glycoprotein 2; testosterone repressed prostate message-2|
|Strain of Origin||129S2/SvPas|
|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.|
|Mutations Made By|| |
Bruce Aronow, Cincinnati Children's Hospital Med Cntr
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.
The average number of mice provided from recovery of our cryopreserved strains is 10. The total number of animals provided,
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