Fancb deficiency causes premature ovarian insufficiency in mice

Abstract

FANCB protein is a major component of the Fanconi anemia (FA) core complex and plays important role in hematopoiesis and germ cell development. Deletion of Fancb gene causes the defect of primordial germ cells (PGCs) development and infertility in male mice. However, it remains unknown whether Fancb is required for female germ cell development. In this study, we found that the fertility of Fancb knockout male mice in C57/ICR mixed backgrounds was not affected. Female Fancb−/− mice were obtained by crossing Fancb+/− females with Fancb−/Y males. The number of PGCs was dramatically decreased in Fancb−/− females. Very few oocytes were observed after birth and primordial follicle pool was completely depleted at 6 weeks of age in Fancb−/− females. However, the remained oocytes from Fancb−/− mice were normal in fertilization and embryonic development from 2-cell to blastocyst stage. We also found that Fancb and Fancl double knockout males were also fertile and the number of sperm in epididymis was not reduced comparable to that of Fancb−/− and Fancl−/− single knockout mice. Taken together, these results demonstrated that Fancb is also essential for female germ cell development. Inactivation of Fancb causes massive germ cell loss and infertility in adult females. We also found that Fancb and Fancl do not act synergistically in regulating germ cell development.

Analysis and Validation of Critical Signatures and Immune Cell Infiltration Characteristics in Doxorubicin-Induced Cardiotoxicity by Integrating Bioinformatics and Machine Learning

“…It has a vital function in hematopoiesis and the development of germ cells. 50 , 51 Some studies have indicated that the FA pathway serves as an indispensable mechanism for the DNA damage response. 52 Further study has shown that FANCB is known as a DNA repair gene.…”

DNAJC21‐related thrombocytopenia in a young adult female

“…Nevertheless, ovarian dys/agenesis, premature ovarian failure has been reported in F I G U R E 3 The Integrative Genomics Viewer (IGV) images of the DNAJC21, c.1155dup, p.Gln386Thrfs*13. other subtypes of IBMFS including Seckel syndrome, Diamond-Blackfan syndrome, and Fanconi anemia (Burroughs et al, 2009;Gansner et al, 2017;Giri et al, 2017;Khincha & Savage, 2016;Savage & Alter, 2009). Fanconi anemia mouse models have demonstrated follicular depletion and interstitial cell hyperplasia similar to premature ovarian insufficiency patients suggesting the role of Fanconi anemia genes in the regulation of germ cell development (Cen et al, 2022). The roles of genes related to other IBMFS on follicular and ovarian development are yet to be elucidated (Fu et al, 2016).…”

Analysis and validation of critical signatures and immune cell infiltration characteristics in doxorubicin-induced cardiotoxicity by integrating bioinformatics and machine learning

“…FANCB, fully de ned as Fanconi anemia complementation group B and known as FAAP95, is an essential constituent of the Fanconi anemia (FA) core complex. It has a vital function in hematopoiesis and the development of germ cells [45,46]. Some studies have indicated that the FA pathway serves as an indispensable mechanism for the DNA damage response [47].…”