We have generated transgenic mice that express angiotensin II (Ang II) fused downstream of enhanced cyan fluorescent protein, expression of which is regulated by the mouse metallothionein promoter. The fusion protein, which lacks a secretory signal, is retained intracellularly. In the present study, RT-PCR, immunoblot analyses, whole animal fluorescent imaging, and fluorescent microscopy of murine embryonic fibroblasts confirm expression of the fusion protein in vivo and in vitro. The transgene is expressed in all tissues tested (including brain, heart, kidney, liver, lung and testes) and radioimmunoassay of plasma samples obtained from transgenic mice indicate no increase in circulating Ang II over wild-type levels, consistent with intracellular retention of the transgene product. Kidneys from transgenic and corresponding wild-type littermates were histologically evaluated and abnormalities in transgenic mice consistent with thrombotic microangiopathy were observed; microthrombosis was frequently observed within the glomerular capillaries and small vessels. In addition, systolic and diastolic blood pressures, measured by telemetry (n = 8 for each group) were significantly higher in transgenic mice as compared to wild-type littermates. Blood pressure of Line A male transgenic mice was 125 ± 1.7 over 97 ± 1.6 compared to 109 ± 1.7 over 83 ± 1.4 in wild-type littermates (systolic over diastolic). In summary, overexpression of an intracellular fluorescent fusion protein of Ang II correlates with elevated blood pressure and kidney pathology. This transgenic model may be useful to further explore the intracellular renin-angiotensin system and its implication in abnormal kidney function and hypertension.
- intracellular angiotensin
- Copyright © 2010, American Journal of Physiology - Heart and Circulatory Physiology