Differential ACE expression among tissues in allele-specific Wistar rat lines

Area of Science:

• Genetics
• Cardiovascular Science
• Renal Science

Background:

• The angiotensin converting enzyme (ACE) gene insertion/deletion polymorphism influences plasma ACE activity and is linked to cardiovascular and renal diseases in humans.
• A similar variation (B/L alleles) in the rat ACE gene suggests a potential animal model for studying these conditions.

Purpose of the Study:

• To investigate the functional consequences of B/L allelic variation in the rat ACE gene.
• To establish and characterize two rat lines (WU-B and WU-L) that are homozygous for the B and L alleles, respectively.
• To explore tissue-specific differences in ACE activity, expression, and function between these rat lines.

Main Methods:

• Developed two rat lines (WU-B and WU-L) homozygous for ACE gene B and L alleles.
• Measured ACE activity in serum, heart, kidney, and aorta homogenates.
• Assessed ACE mRNA expression and performed immunohistochemistry in key tissues.
• Evaluated functional ACE activity in aortic rings using vasoconstrictor responses to Angiotensin I and II.

Main Results:

• WU-B rats exhibited two-fold higher serum, heart, and kidney ACE activity and kidney mRNA expression compared to WU-L rats.
• Immunohistochemistry revealed distinct tubular ACE expression patterns, with higher staining in WU-B rats.
• Aorta showed twofold higher ACE activity and mRNA expression in WU-L rats, yet WU-B rats demonstrated greater functional Angiotensin I to Angiotensin II conversion.
• These findings suggest allele-specific functional differences in ACE activity and potential involvement of other regulatory factors.

Conclusions:

• The newly developed WU-B and WU-L rat lines display significant tissue-specific differences in ACE expression and activity.
• These distinct rat models provide a valuable experimental tool for elucidating the pathophysiological roles of ACE allelic variations in renal and cardiovascular diseases.