Mkrn1-flox Mouse

Mkrn1, also called RNF61, is a member of the RING finger protein family and functions as an E3 ubiquitin ligase. It is involved in multiple biological processes and associated with various diseases. It participates in pathways like TGF-β signalling, which is crucial for cell growth, differentiation, and apoptosis [1].

In colorectal cancer, MKRN1 expression is elevated compared to paracancerous tissues. Conditional knockout mice with intestinal knockout of MKRN1 showed greatly reduced intestinal lesions and metastatic liver microlesions, indicating that high MKRN1 levels promote TGF-β signalling through ubiquitination and degradation of SNIP1, facilitating CRC metastasis [1].

In triple-negative breast cancer, SF3A2 promotes TNBC progression by regulating the alternative splicing of MKRN1 and promoting the expression of the oncogenic isoform MKRN1-T1 [2].

In renal clear cell carcinoma, MKRN1 is lowly expressed, and its overexpression inhibits cell proliferation by arresting the cell cycle, suggesting it acts as a tumor suppressor [3].

In cervical cancer, MKRN1 expression is up-regulated, and its knockdown inhibits cell proliferation, migration, and invasion [4].

In conclusion, Mkrn1 plays diverse roles in different diseases. Its functions range from promoting cancer metastasis in colorectal and cervical cancers to acting as a tumor suppressor in renal clear cell carcinoma. The use of gene knockout and conditional knockout mouse models has been crucial in revealing these functions, providing valuable insights into disease mechanisms and potential therapeutic targets.