Meis1-KO Mouse

Meis1, short for Myeloid ecotropic viral integration site 1, is a homeobox-containing transcription factor belonging to the three-amino acid loop extension (TALE) family of homeodomain (HD) proteins. It binds to DNA in a sequence-specific manner and is involved in multiple biological processes, including cell proliferation, differentiation, and embryonic development. It is highly associated with Hox genes and their cofactors, regulating various intracellular signaling pathways [1,4,5].

In leukemia, increased Meis1 expression has been observed in acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) patients, and leukemic blast samples with high Meis1 content show resistance to conventional chemotherapy, suggesting its oncological role [5]. In colorectal cancer, the ELFN1-AS1/EZH2/DNMT3a axis downregulates Meis1, promoting tumorigenesis and oxaliplatin resistance. Preventing DNA damage repair by Meis1 can enhance CRC cell sensitivity to oxaliplatin [2]. In restless legs syndrome (RLS), the MEIS1 gene shows a strong genetic association. Although the protein's function directly linked to an RLS biological pathway remains unknown, work in C. elegans indicates a link between the MEIS1 ortholog and iron homeostasis, which is relevant as CNS iron insufficiency is thought to cause RLS [3]. In cardiovascular regeneration, inhibition of Meis1 expression increases the proliferative capacity of neonatal mouse cardiomyocytes, while overexpression reduces the length of the cardiomyocyte proliferative window. Also, downregulation of a circular RNA downstream of Meis1 in cardiomyocytes promotes angiogenesis and myocardial blood supply [4]. In chronic kidney disease (CKD), increased Meis1 expression in the kidney nucleus is negatively correlated with serum creatinine. Fibroblast-specific knock-in of Meis1 inhibits myofibroblast activation, attenuating renal fibrosis and kidney dysfunction, as Meis1 targets protein tyrosine phosphatase receptor J (Ptprj) to block renal fibrosis [6].

In summary, Meis1 plays crucial roles in various biological processes and diseases. Through gene knockout or conditional knockout mouse models and other functional studies, its role in processes like cell proliferation in cancer, iron homeostasis in RLS, and cardiovascular and kidney regeneration has been revealed. These model-based studies contribute significantly to understanding the underlying mechanisms of related diseases, potentially providing new therapeutic targets [1-5,8].