Xrn1-flox Mouse

Xrn1, an exoribonuclease, plays a crucial role in RNA decay, executing the last step of mRNA degradation in the cytoplasm along the 5'-3' direction [3,4,5,9]. It is involved in multiple pathways such as dsRNA sensing, mRNA decapping and decay, and is associated with important biological processes like reproduction, metabolism, and immune response [1,2,3,5,6,7,8]. Genetic models, especially knockout models, are valuable for studying its functions.

In interferon-activated cancer cells, Xrn1 deletion causes PKR-dependent cell lethality, highlighting its role as a negative regulator of the PKR pathway [1,2]. In Macrobrachium nipponense, knockdown of Mn-XRN1 accelerates ovarian development, indicating its inhibitory effect on ovarian reproduction [5]. In forebrain-specific Xrn1 conditional knockout (Xrn1-cKO) mice, obesity, leptin resistance, hyperglycemia, hyperphagia, and decreased energy expenditure occur, suggesting that XRN1 in the hypothalamus is critical for metabolic homeostasis [8]. Targeting XRN1 in cancer cells can also potentiate the efficacy of cancer immunotherapy as its depletion activates IFN signaling and the viral defense pathway [7].

In conclusion, Xrn1 is essential for RNA decay and is involved in diverse biological processes. Gene knockout and conditional knockout mouse models have revealed its significance in cancer, reproduction, and metabolic diseases. These findings offer potential therapeutic targets for related diseases and enhance our understanding of the underlying molecular mechanisms.