Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: Core Binding Factor β Knockdown Alters Ovarian Gene Expression and Function in the Mouse. Wilson K et al. (2016) Core Binding Factor (CBF) is a heterodimeric transcription factor complex composed of a DNA-binding subunit, one of three RUNX factors, and a non-DNA binding subunit, CBFβ. CBFβ is critical for DNA binding and stability of the CBF transcription factor complex. In the ovary, the LH surge increases the expression of Runx1 and Runx2 in periovulatory follicles, implicating a role for CBFs in the periovulatory process. The present study investigated the functional significance of CBFs (RUNX1/CBFβ and RUNX2/CBFβ) in the ovary by examining the ovarian phenotype of granulosa cell-specific CBFβ knockdown mice; CBFβ f/f * Cyp19 cre. The mutant female mice exhibited significant reductions in fertility, with smaller litter sizes, decreased progesterone during gestation, and fewer cumulus oocyte complexes collected following induced superovulation. RNA sequencing and transcriptome assembly revealed altered expression of over 200 mRNA transcripts in granulosa cells of Cbfb knockdown mice following hCG stimulation in vitro. Among the effected transcripts are known regulators of ovulation and luteinization including Sfrp4, Sgk1, Lhcgr, Prlr, Wnt4, and Edn2, as well as many genes not yet characterized in the ovary. Cbfβ knockdown mice also exhibited decreased expression of key genes within corpora lutea and morphological changes in ovarian structure, including the presence of large antral follicles well into the luteal phase. Overall, these data suggest a role for CBFs as significant regulators of gene expression, ovulatory processes, and luteal development in the ovary.//////////////////

Species: mouse
Mutation name:
type: null mutation
fertility: subfertile
Comment: Core Binding Factor β expression in ovarian granulosa cells is essential for female fertility. Lee-Thacker S et al. (2018) Core Binding Factor beta (CBFβ) is a non-DNA binding partner of all RUNX proteins and critical for transcription activity of CBF transcription factors (RUNXs/CBFβ). In the ovary, the expression of Runx1 and Runx2 is highly induced by the LH surge in ovulatory follicles, while Cbfb is constitutively expressed. To investigate the physiological significance of CBFs in the ovary, the present study generated two different conditional mutant mouse models in which granulosa cell expression of Cbfb and Runx2 was reduced by Cre recombinase driven by an Esr2 promoter. Cbfbgc-/- and Cbfbgc-/- * Runx2gc+/- mice exhibited severe subfertility and infertility, respectively. In the ovaries of both mutant mice, follicles develop normally, but the majority of preovulatory follicles failed to ovulate either in response to hCG administration in PMSG-primed immature animals or after the LH surge at five months of age. Morphological and physiological changes in the corpus luteum of these mutant mice revealed the reduced size, progesterone production, and vascularization, as well as excessive lipid accumulation. In granulosa cells of periovulatory follicles and corpora lutea of these mice, the expression of Edn2, Ptgs1, Lhcgr, Sfrp4, Wnt4, Ccrl2, Lipg, Saa3, and Ptgfr was also drastically reduced. In conclusion, the present study provided in vivo evidence that CBFβ plays an essential role in female fertility by acting as a critical cofactor of CBF transcription factor complexes which regulate the expression of specific key ovulatory and luteal genes, thus coordinating the ovulatory process and luteal development/function in mice.//////////////////