Search

Heterozygous mutation of CHD7 gene causes a severe developmental disorder called CHARGE syndrome. In order to further explore the expression and function of Chd7 in vivo, we generated a Chd7-P2A-iCreERT2-P2A-tdTomato (in short, Chd7-CT-tdT) knockin mouse line using the CRISPR/Cas9 technology. The specificity and efficiency of two knockin genetic elements were validated. The Chd7-CT-tdT reporter gene could accurately reflect both the dynamic expression pattern of endogenous Chd7 during neurodevelopment and cell-type specific expression in the brain and eye. The recombination efficiency of Chd7-CT-tdT in postnatal cerebellum is very high. Moreover, lineage tracing experiment showed that Chd7 is expressed in intestinal stem cells. In summary, the newly constructed Chd7-CT-tdT mouse line provide a useful tool to study the function of Chd7., (© 2023 Wiley Periodicals LLC.)

Background: Chromodomain helicase DNA-binding protein 7 (CHD7), which is associated with CHARGE (Coloboma, Heart defect, Atresia choanae, Restricted growth, Genital hypoplasia and Ear abnormality) syndrome is an important regulator in many vital developmental processes. However, its role during oocyte development remains unknown., Methods: We screened the Gene Expression Omnibus (GEO) database for expression levels of CHD7 during folliculogenesis. We generated a conditional knockout (cKO) mouse strain with oocyte-specific deletion of CHD7 ( Gdf9-Cre:Chd7 f/f ) using the Cre-loxP approach. Evaluation of follicle numbers and reproductive ability was then conducted. In addition, granulosa cell (GC) apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and cleaved caspase-3, using immunohistochemistry (IHC) and immunofluorescence (IF). GC proliferation was measured by Ki67 staining as evaluated by IHC., Results: In our study, we demonstrated that CHD7 has high expression throughout all developmental stages of the oocyte. We found that deletion of Chd7 in oocytes can cause infertility or sub-fertility in female mice and is associated with decreased follicle numbers at all stages. In addition, we found that GC apoptosis was significantly higher in cKO mice., Conclusions: To our knowledge, our study has been the first to show that CHD7 plays a specific role during oogenesis. Our findings provide new insights into CHD7-related infertility., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://atm.amegroups.com/article/view/10.21037/atm-22-609/coif). The authors have no conflicts of interest to declare., (2022 Annals of Translational Medicine. All rights reserved.)