Agtrap-flox Mouse

Agtrap, also known as Angiotensin II Receptor-Associated Protein (ATRAP), is a molecule that specifically interacts with the carboxyl-terminal domain of the Ang II type 1 receptor (AT1R) [1]. It has been shown to suppress Ang II-mediated pathological responses in cardiovascular cells by promoting AT1R internalization. The AGTRAP-PLOD1 locus is a conserved gene cluster containing several blood pressure regulatory genes, suggesting its involvement in blood pressure regulation [2].

In a study with Agtrap-deficient (Agtrap(-/-)) mice, under dietary high fat loading, these mice displayed systemic metabolic dysfunction, including increased pad fat accumulation, hypertension, dyslipidemia, and insulin resistance, along with adipose tissue inflammation. Conversely, subcutaneous transplantation of donor fat pads overexpressing ATRAP derived from Agtrap transgenic mice to Agtrap(-/-) recipient mice improved the systemic metabolic dysfunction. This indicates that Agtrap plays a protective role against insulin resistance [3]. In another study, prehypertensive losartan-treated spontaneously hypertensive rats (SHRs) showed hypomethylation of Agtrap and upregulation of ATRAP expression in the myocardium, which was associated with long-term inhibition of left ventricular hypertrophy (LVH) [4].

In conclusion, Agtrap plays crucial roles in metabolic regulation, protecting against insulin resistance, and in cardiovascular function, being associated with the inhibition of left ventricular hypertrophy. The use of Agtrap-deficient and transgenic mouse models has been instrumental in revealing these functions, providing insights into potential therapeutic targets for metabolic and cardiovascular diseases.