Rnh1-flox Mouse

Rnh1, also known as ribonuclease inhibitor 1 or angiogenin inhibitor 1, is a ubiquitously expressed leucine-rich repeat protein. It is an accessory part of the translation machinery. Rnh1 interacts with angiogenin (ANG) to inhibit its ribonucleolytic activity, and can also bind to 40S ribosomes to control translation. It is involved in multiple biological processes such as translation regulation, inflammasome activation, and iron homeostasis [1,2,7].

In mouse models, inactivation of rnh1 causes embryonically lethal anemia [5]. In humans, loss-of-function of RNH1 is associated with a multiorgan developmental disease including congenital cataracts, global developmental delay, myopathy, psychomotor deterioration, seizures, and periodic anemia. Patient fibroblasts with RNH1 deficiency are more sensitive to RNase A exposure [5]. Biallelic variants in RNH1 confer susceptibility to a subtype of acute, necrotizing encephalopathy in children [6]. In bladder cancer, low RNH1 expression is related to enhanced invasion and metastasis, and it can also predict immunotherapy response [3]. In lung adenocarcinoma, E2F1 binds to the RNH1 promoter to inhibit its expression, promoting tumor development [4].

In conclusion, Rnh1 plays essential roles in translation, cell development, and homeostasis. Studies on Rnh1 knockout mouse models have revealed its significance in various disease conditions such as anemia, multiorgan developmental diseases, and certain types of encephalopathy. Understanding Rnh1 provides insights into disease mechanisms and may offer potential therapeutic targets.