Agtr1b-KO Mouse

Agtr1b, the angiotensin type 1B receptor gene, is part of the renin-angiotensin system which plays a crucial role in regulating blood pressure, fluid and electrolyte balance. Rodents uniquely carry this gene along with Agtr1a, both encoding angiotensin type 1 (AT1) receptors [2,3].

Gene-targeting experiments in mice have provided key insights into Agtr1b function. In Agtr1b -/- mice, high transcriptional activity was seen in adrenal zona glomerulosa cells and the testis, while low activity was detected in anterior pituitary cells and choroidal plexus vessel walls. These mice showed no abnormal phenotypes, suggesting that AT1A receptors can substitute for AT1B receptors or that non-AT1, non-AT2 receptors may exist for angiotensin action [1]. In contrast, Agtr1a -/-; Agtr1b -/- double mutant mice had severe phenotypes similar to angiotensinogen nullizygotes, including low body weight gain, marked hypotension, and abnormal kidney morphology, indicating that major biological functions of endogenous angiotensin are mediated by AT1 receptors [2]. Also, Agtr1b -/- mice are healthy without an abnormal phenotype, but Agtr1a -/-Agtr1b -/- mice have diminished growth, vascular thickening in the kidney, and atrophy of the inner renal medulla [3].

In summary, model-based research, especially using Agtr1b knockout mouse models, reveals that Agtr1b, along with Agtr1a, is important for the normal physiological functions mediated by the renin-angiotensin system. These studies highlight its significance in maintaining normal growth, kidney structure, and blood pressure regulation, contributing to our understanding of related diseases such as hypertension and kidney disorders [1,2,3].

References:

1. Chen, X, Li, W, Yoshida, H, Matsusaka, T, Ichikawa, I. . Targeting deletion of angiotensin type 1B receptor gene in the mouse. In The American journal of physiology, 272, F299-304. doi:. https://pubmed.ncbi.nlm.nih.gov/9087671/

2. Tsuchida, S, Matsusaka, T, Chen, X, Inagami, T, Ichikawa, I. . Murine double nullizygotes of the angiotensin type 1A and 1B receptor genes duplicate severe abnormal phenotypes of angiotensinogen nullizygotes. In The Journal of clinical investigation, 101, 755-60. doi:. https://pubmed.ncbi.nlm.nih.gov/9466969/

3. Oliverio, M I, Kim, H S, Ito, M, Smithies, O, Coffman, T M. . Reduced growth, abnormal kidney structure, and type 2 (AT2) angiotensin receptor-mediated blood pressure regulation in mice lacking both AT1A and AT1B receptors for angiotensin II. In Proceedings of the National Academy of Sciences of the United States of America, 95, 15496-501. doi:. https://pubmed.ncbi.nlm.nih.gov/9860997/