B6.129P2-Ace^tm3Unc/J

Stock number: 002689
Product name: Ace duplication
Research areas: Cardiovascular Research

Description

These mice carry a targeted duplication mutation at the Ace locus characterized by increased angiotensin-converting enzyme activity.

Detailed description

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.

Development

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

Symbol: Ace^tm3Unc
Name: targeted mutation 3, University of North Carolina
MGI accession ID: MGI:2155951
Generation method: Targeted
Attributes: Inserted expressed sequence
Marker symbol: Ace
Marker name: angiotensin I converting enzyme (peptidyl-dipeptidase A) 1
Chromosome: 11
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.