Nudt13-KO Mouse

Nudt13, a mammalian gene, encodes a protein with a sequence motif characteristic of the NADH pyrophosphohydrolase subfamily of Nudix hydrolases. It functions as a mitochondrial Nudix hydrolase, efficiently hydrolyzing NADH to NMNH and AMP, and NADPH to NMNH and 2',5'-ADP, thus potentially regulating the concentration of mitochondrial reduced pyridine nucleotide cofactors and the NAD(P)+/NAD(P)H ratio [1].

In colorectal cancer, Nudt13 is identified as a critical suppressor. Elevated Nudt13 expression impedes CRC cell proliferation under hypoxic conditions and inhibits CRC initiation by upregulating PKM1. Mechanistically, it directly binds and stabilizes PKM1 protein by reducing its poly ADP-ribosylation, inducing an oxidative phosphorylation phenotype in CRC cells. Spatiotemporal knockout of Nudt13 in mice enhances intestinal tumorigenesis, which can be suppressed by a PARP1 inhibitor [2]. Also, in CRC, Nudt13 is among the genes associated with survival time in the most aggressive form of the disease, potentially serving as a diagnostic target [3,5]. Additionally, genetically-predicted gene expression of Nudt13 in multiple tissues, including subcutaneous adipose tissue, is associated with uterine fibroids [4].

In conclusion, Nudt13 plays a crucial role in regulating mitochondrial pyridine nucleotide cofactors. Its function is also significant in diseases such as colorectal cancer and potentially uterine fibroids. Studies using gene knockout mouse models in CRC have revealed its tumor-suppressing role, providing insights into disease mechanisms and potential therapeutic targets.

References:

1. Abdelraheim, Salama R, Spiller, David G, McLennan, Alexander G. . Mouse Nudt13 is a Mitochondrial Nudix Hydrolase with NAD(P)H Pyrophosphohydrolase Activity. In The protein journal, 36, 425-432. doi:10.1007/s10930-017-9734-x. https://pubmed.ncbi.nlm.nih.gov/28755312/

2. Lin, Jinlong, Yin, Yixin, Cao, Jinghua, Xie, Dan, Wang, Fengwei. 2025. Nudix Hydrolase 13 Impairs the Initiation of Colorectal Cancer by Inhibiting PKM1 ADP-Ribosylation. In Advanced science (Weinheim, Baden-Wurttemberg, Germany), 12, e2410058. doi:10.1002/advs.202410058. https://pubmed.ncbi.nlm.nih.gov/39921866/

3. Hajebi Khaniki, Saeedeh, Shokoohi, Farhad, Esmaily, Habibollah, Kerachian, Mohammad Amin. 2023. Analyzing aberrant DNA methylation in colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients. In Scientific reports, 13, 22104. doi:10.1038/s41598-023-47377-1. https://pubmed.ncbi.nlm.nih.gov/38092774/

4. Edwards, Todd L, Giri, Ayush, Hellwege, Jacklyn N, Roden, Dan M, Velez Edwards, Digna R. 2019. A Trans-Ethnic Genome-Wide Association Study of Uterine Fibroids. In Frontiers in genetics, 10, 511. doi:10.3389/fgene.2019.00511. https://pubmed.ncbi.nlm.nih.gov/31249589/

5. Khaniki, Saeedeh Hajebi, Shokoohi, Farhad, Esmaily, Habibollah, Kerachian, Mohammad Amin. 2023. Analyzing aberrant DNA methylation in Colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients. In Research square, , . doi:10.21203/rs.3.rs-2957915/v1. https://pubmed.ncbi.nlm.nih.gov/37397988/