Foxj3, a member of the Forkhead Box gene family, is involved in multiple biological processes. It functions as a transcription factor and is associated with pathways like mitochondrial biogenesis, epithelial-mesenchymal transition, and thermogenesis. Its study using genetic models, such as knockout (KO) mouse models, has been crucial in understanding its role in health and disease [3].

In adipose tissue, cold exposure and β-adrenergic agonists stimulate Foxj3 expression. Adipose-specific Foxj3 knockout impairs brown fat thermogenic function, leading to obesity, increased fasting blood glucose, and hepatic steatosis. It also inhibits the browning of inguinal white adipose tissue. Conversely, overexpression of Foxj3 in adipose tissue increases energy expenditure and improves metabolism. Mechanistically, Foxj3 stimulates the expression of PGC-1α and UCP1, promoting energy expenditure [1]. In breast cancer cells, Foxj3 over-expression affects cell proliferation, migration, and invasion by modulating Snail expression [2]. In colorectal cancer cells, the miR-27a/FOXJ3 axis dysregulates mitochondrial homeostasis [4]. In neuroblastoma, FOXJ3 functions as a tumor suppressor, with higher expression in low-risk patients, and its overexpression reduces cell proliferation and migration [5]. In skeletal muscle, Foxj3 mutant mice have fewer Type I slow-twitch myofibers and impaired muscle regeneration, as Foxj3 transcriptionally activates Mef2c [6]. In spermatogenesis, conditional knockout of Foxj3 in spermatogonia causes Sertoli-cell-only syndrome, while its knockout in spermatocytes leads to meiotic arrest [7].

In summary, Foxj3 plays diverse and crucial roles in multiple biological processes. Studies using KO and conditional knockout (CKO) mouse models have revealed its importance in fat thermogenesis, cancer development, muscle function, and spermatogenesis. These findings provide potential therapeutic targets for treating obesity, metabolic diseases, and various cancers.