Bright Cells, and Inefficient Enzymatic Activity in a Renin Hypomorph Mouse

Area of Science:

• Renal physiology and endocrinology
• Cardiovascular research
• Genetics and molecular biology

Background:

• Juxtaglomerular (JG) cells regulate blood pressure and fluid balance through renin secretion.
• Under stress, renin-producing cells can expand, leading to arteriolar hypertrophy.
• Isolating rare renin cells is crucial for studying their identity, plasticity, and function.

Purpose of the Study:

• To develop a mouse model for fluorescently labeling and tracking renin-expressing cells.
• To investigate renin cell plasticity and the mechanisms of concentric arteriolar hypertrophy.
• To provide a tool for studying renin protein regulation.

Main Methods:

• Generation of a bicistronic mouse model (Ren1 ^ctdTomato) under the control of the Ren1 ^c locus.
• Analysis of tdTomato reporter expression in heterozygous (Het) and homozygous (Homo) mice under basal and stimulated conditions (captopril + low-salt diet).
• Assessment of renin expression, blood pressure, plasma angiotensin I levels, kidney function, and histology in Homo mice.

Main Results:

• tdTomato reporter accurately labeled renin cells in Het mice under basal and stimulated conditions.
• Homo mice showed widespread tdTomato signal, arteriolar hypertrophy, reduced renin immunostaining, but increased kidney Ren1 mRNA and circulating renin.
• Homo mice exhibited lower blood pressure, reduced plasma angiotensin I, interstitial fibrosis, and compromised kidney function, indicating a renin hypomorphic state.

Conclusions:

• The Ren1 ^ctdTomato mouse model enables effective tracking and isolation of renin-expressing cells.
• Homozygous mice display a renin hypomorphic phenotype with concentric arteriolar hypertrophy, mimicking conditions of RAS inhibition.
• This model is valuable for studying renin cell biology, arteriolar remodeling, and factors influencing renin protein processing and release.