B6.129P2-Agt^tm1Unc/J

Stock number: 002681
Product name: Agt zero-copy
Research areas: Cardiovascular Research, Endocrine Deficiency Research, Internal/Organ Research

Description

These Agt knock-out mice represent the “zero-copy” number of Agt in a study examining the effect of gene copy number on pathological changes in adult kidney and blood vessels.

Detailed description

Newborn homozygotes for the targeted disruption of Agt have no obvious pathological defects although only a few survive to adulthood. There are pathological changes in adult kidney and blood vessels. The effect of gene copy number was examined using these mice and C57BL/6J-TgH(Agtdup)1Unc (Stock No. 002690). Plasma angiotensinogen levels increase progressively, although not linearly, from zero in zero-copy (Agt^tm1Unc/Agt^tm1Unc) mice to 145% of normal in four-copy (Agt^dup/Agt^dup) mice. Mice of all genotypes are normal at birth, but most zero-copy animals show pathological changes as adults, the kidneys are normal in the other genotypes. The blood pressures of the one-copy through four-copy animals show significant and almost linear increases of approximately 8mmHg per gene copy despite their normal compensatory mechanisms being intact.

Allele

Symbol: Agt^tm1Unc
Name: targeted mutation 1, University of North Carolina
MGI accession ID: MGI:1857121
Generation method: Targeted
Attributes: Null/Knockout
Marker symbol: Agt
Marker name: angiotensinogen (serpin peptidase inhibitor, clade A, member 8)
Chromosome: 8
Strain of origin: 129P2/OlaHsd
Molecular note: A genomic fragment within exon 2 that codes for 114 amino acids of the encoded protein was replaced with a neomycin selection cassette. Radioimmunoassay tests confirmed that no protein was detectable in plasma of homozygous mice.
General note: Human AGT and renin genes can complement the effects of the mouse null mutation (J:39934).