These mice carry a targeted duplication mutation at the Ace locus characterized by increased angiotensin-converting enzyme activity.
Dr. Oliver Smithies, University of North Carolina at Chapel Hill
The entire angiotensin converting gene is duplicated in this strain by homologous recombination (gap repair gene targeting). Mice that are heterozygous for this mutation have three functional genes. Mice that are homozygous for this mutation have four functional genes. This permits examination of the effects of having two (wildtype), three or four functional copies of the targeted gene in its normal chromosomal location. Serum ACE activities increased progressively from 62% in one copy mice to 144% of normal in three copy animals. Blood pressures did not differ significantly; however, heart rates, heart weights and renal tubulointerstitial volumes decreased significantly with increasing copy number. This mutant mouse strain may be useful in studies of cardiovascular and renal disease.
This allele was made in the laboratory of Dr. Oliver Smithies at the University of North Carolina,Chapel Hill. Duplication of the targeted gene was generated by a special form of gap-repair targeting that tandemly duplicates the whole of a gene together with the 5' and 3' flanking regions. The targeting vector, containing neomycin resistance and herpes simplex virus thymidine kinase genes was used to insert two copies of the gene, separated by the neomycin resistance gene, into the endogenous locus. The construct was electroporated into 129P2/OlaHsd derived E14TG2a (BK4 subline) embryonic stem (ES) cells. Correctly targeted ES cells were injected into C57BL/6J blastocysts. The resulting male chimeric animal was crossed to C57BL/6J female mice, and then backcrossed to the same for 6 generations.
|Allele Name||targeted mutation 3, University of North Carolina|
|Allele Type||Targeted (Inserted expressed sequence)|
|Allele Synonym(s)||Tg(Acedup)2Unc; TgH(Acedup)2Unc|
|Gene Symbol and Name||Ace, angiotensin I converting enzyme (peptidyl-dipeptidase A) 1|
|Promoter||Ace, angiotensin I converting enzyme (peptidyl-dipeptidase A) 1, mouse, laboratory|
|Strain of Origin||129P2/OlaHsd|
|Molecular Note||A gap-repair type targeting vector was used to induce a gene duplication. Two tandem copies of the gene were present in the final allele. Protein activity measurments correlated with gene dosage in serum and lung tissue.|
|Mutations Made By|| |
Dr. Oliver Smithies, University of North Carolina at Chapel Hill
When maintaining a live colony, this strain is maintained by homozygous sibling matings. Expected coat color from breeding:Black
When using the Ace duplication mouse strain in a publication, please cite the originating article(s) and include JAX stock #002689 in your Materials and Methods section.
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