Hsf2bp-KO Mouse

Hsf2bp, as its name implies, is a binding protein of HSF2. It is involved in multiple biological processes. It participates in the heat shock response (HSR)-related pathways and is associated with homologous recombination, which is crucial for DNA repair, and has significance in processes like spermatogenesis and folliculogenesis [1,2,3,4,5]. Genetic models such as hsf2bp-KO and hsf2bp-TG mouse models have been instrumental in studying its functions [1].

In hsf2bp-KO and hsf2bp-TG mouse models, Hsf2bp was found to play a protective role in acute liver injury. It reduced hepatocyte death, ameliorated inflammation, and improved liver function in APAP-or D-GalN/LPS-induced liver injury, and increased the survival rate of hsf2bp-TG mice after APAP administration. It does this by upregulating the expression of HSF2 and HSP70 and inhibiting the activation of Jnk1/2 and P38 MAPK [1]. In male mice, inactivation of Hsf2bp leads to infertility due to a severe homologous recombination defect during spermatogenesis [4]. In female mice, a missense variant in Hsf2bp (S167L) reduces fertility, and meiocytes with this variant show decreased staining of Hsf2bp and its interactor BRME1 at recombination nodules, and a reduced number of RAD51/DMC1 foci, leading to a lower frequency of crossovers [5].

In conclusion, Hsf2bp is essential for processes like spermatogenesis, folliculogenesis, and protection against acute liver injury. The use of hsf2bp-KO and hsf2bp-TG mouse models has revealed its role in these processes, highlighting its importance in understanding the mechanisms of infertility and liver injury [1,4,5].

References:

1. Bi, Jianbin, Zhang, Jia, Ke, Mengyun, Lv, Yi, Wu, Rongqian. 2022. HSF2BP protects against acute liver injury by regulating HSF2/HSP70/MAPK signaling in mice. In Cell death & disease, 13, 830. doi:10.1038/s41419-022-05282-x. https://pubmed.ncbi.nlm.nih.gov/36167792/

2. Ghouil, Rania, Miron, Simona, Sato, Koichi, Zelensky, Alex N, Zinn-Justin, Sophie. 2023. BRCA2-HSF2BP oligomeric ring disassembly by BRME1 promotes homologous recombination. In Science advances, 9, eadi7352. doi:10.1126/sciadv.adi7352. https://pubmed.ncbi.nlm.nih.gov/37889963/

3. França, Monica Malheiros, Mendonca, Berenice Bilharinho. 2021. Genetics of ovarian insufficiency and defects of folliculogenesis. In Best practice & research. Clinical endocrinology & metabolism, 36, 101594. doi:10.1016/j.beem.2021.101594. https://pubmed.ncbi.nlm.nih.gov/34794894/

4. Brandsma, Inger, Sato, Koichi, van Rossum-Fikkert, Sari E, Kanaar, Roland, Zelensky, Alex N. . HSF2BP Interacts with a Conserved Domain of BRCA2 and Is Required for Mouse Spermatogenesis. In Cell reports, 27, 3790-3798.e7. doi:10.1016/j.celrep.2019.05.096. https://pubmed.ncbi.nlm.nih.gov/31242413/

5. Felipe-Medina, Natalia, Caburet, Sandrine, Sánchez-Sáez, Fernando, Veitia, Reiner A, Pendás, Alberto M. 2020. A missense in HSF2BP causing primary ovarian insufficiency affects meiotic recombination by its novel interactor C19ORF57/BRME1. In eLife, 9, . doi:10.7554/eLife.56996. https://pubmed.ncbi.nlm.nih.gov/32845237/