Lbh, or Limb-bud and Heart, is a transcription co-factor that has been implicated in multiple biological processes. It is associated with the WNT pathway and is important in development [1,3]. Genetic models, such as knockout (KO) mouse models, have been valuable in studying its functions.

In a Lbh-null mouse model, it was found that while Lbh deletion did not affect the differentiation and early development of cochlear hair cells (HCs), it led to progressive hearing loss, with stereocilia bundle degeneration and HC loss starting from postnatal day 12. RNA-seq analysis in Lbh-null outer HCs showed gene enrichment in processes related to transcriptional regulation, cell cycle, DNA damage/repair, and autophagy, along with dysregulation of Wnt and Notch pathway-related genes [2]. In triple-negative breast cancer (TNBC) cell models, depletion of LBH triggered apoptotic cell death both in vitro and in vivo, and led to S-G2M cell cycle delays. Mechanistically, LBH loss caused replication stress due to DNA replication fork stalling [1].

In conclusion, Lbh is crucial for the survival of cochlear hair cells and plays a role in maintaining genome integrity in TNBC cells. The use of Lbh KO mouse models has provided insights into its functions in these specific disease-related biological processes, such as hearing loss and TNBC progression.