Mice heterozygous for Sod2tm1Leb and homozygous for Ldlrtm1Her may be predisposed to atherosclerosis.
Dr. Jan L. Breslow, Rockefeller University
Independently, mice that are homozygous for this MnSOD mutation (Sod2tm1Leb) allele exhibit postnatal lethality and exhibit anemia, degeneration of neurons in the basal ganglia and brainstem, progressive motor disturbances, and myocardial injury. Individual LDLR homozygous mutants are predisposed to atherosclerosis. When mutant mice are homozygous for both alleles, they die in utero. Mice heterozygous for the Sod2 mutation and homozygous for the LDLR are viable and fertile. The mice may be useful in studies of diabetes, metabolism, hyperglycemia, atherosclerosis, and hypercholesterolemia, and oxidative stress.
The Ldlrtm1Her mutation was made by Dr. Robert Hammer and Joachim Herz (HHMI, University of Texas Southwestern Medical Center). Briefly, a targeting vector was used to insert a neo cassette into exon 4. The vector was electroporated into 129S7/SvEvBrd-derived AB1 embryonic stem (ES) cells. Chimeric mice were bred to C57BL/6J, and the strain was made congenic on a C57BL/6J genetic background at The Jackson Laboratory (Stock No. 002207). The Sod2tm1Leb was created by Dr. Russell Lebovitz (Baylor College of Medicine) by replacing exons 1-2 with a PGK-HPRT minigene. The targeting vector was electroporated into 129S7/SvEvBrd-derived AB2.1 and then maintained on a congenic genetic background at The Jackson Laboratory (Stock No. 002973). To generate the double mutant strain, Stock No. 002207 mice were bred with Stock No. 002973 mice in the laboratory of Dr. Jan Breslow at The Rockefeller University. Double mutant mice were then backcrossed to C57BL/6J for approximately 7 generations prior to arrival at The Jackson Laboratory. The donating investigators indicate that 103/104 microsatellite markers indicate C57BL/6J background. The single exception is D17Mit143.2.
|Allele Name||targeted mutation 1, Joachim Herz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||LDLR KO; LDLR-; LDLr-KO; LDLr0; LDLrKO; Ldlrtm1Her|
|Gene Symbol and Name||Ldlr, low density lipoprotein receptor|
|Gene Synonym(s)||FH; FHC; LDLCQ2; LDLRA|
|Site of Expression||Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.|
|Strain of Origin||129S7/SvEvBrd-Hprt<+>|
|General Note||When used in bone marrow transplant into Ldlrtm1Her homozygous mice, Abca1tm1Jdm Abcg1tm1Dgen homozygous cells accelerate the development of atherosclerosis. (J:130777) |
Phenotypic Similarity to Human Syndrome: Type 1 Diabetic Macrovascular Disease J:174983.
|Molecular Note||Insertion of a neomycin resistance cassette into exon 4. The authors predict that the targeted allele would encode a truncated non-functional protein that will not bind LDL, and that lacks a membrane spanning segment. Immunoblot analysis of liver membranes detected a truncated protein in homozygous mutant animals.|
|Mutations Made By|| |
Dr. Joachim Herz, Univ of Texas Southwest Med Ctr Dallas
|Allele Name||targeted mutation 1, Russell M Lebovitz|
|Allele Type||Targeted (Null/Knockout)|
|Allele Synonym(s)||SOD2m1BCM; Sod2-; Sod2mlbcm|
|Gene Symbol and Name||Sod2, superoxide dismutase 2, mitochondrial|
|Gene Synonym(s)||IPO-B; IPOB; MGC:6144; MNSOD; MVCD6; Mn-SOD; MnSOD; Sod-2; Sod-2; manganese SOD; manganese superoxide dismutase|
|Strain of Origin||129S7/SvEvBrd-Hprt |
|Molecular Note||A human HPRT minigene driven by the PGK promoter replaced exons 1 and 2, and sequences approximately 500 bp immediately 5' of exon 1. The replaced region encodes the transcription and translation start sites, the mitochondrial targeting sequence, and one of three histidines that bind directly to the manganese cofactor. Northern blot analysis of brain did not detect mRNA in homozygous mutant mice. Enzyme activity assays of heart did not detect active protein in homozygous mutant mice.|
|Mutations Made By|| |
Dr. Russell Lebovitz, SUMA Partners
When maintaining a live colony, these mice are bred as heterozygous for the Sod2 mutation and homozygous for the Ldlr mutation.
|Please inquire about possible genotypes.|
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