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Sperm proteins undergo post-translational modifications during sperm transit through the epididymis to acquire fertilizing ability. We previously reported that the genomic region coding Pate family genes is key to the proteolytic processing of the sperm membrane protein ADAM3 and male fertility. This region contains nine Pate family genes (Pate5-13), and two protein-coding genes (Gm27235 and Gm5916), with a domain structure similar to Pate family genes. Therefore, in this study, we aimed to identify key factors by narrowing the genomic region. We generated three knockout (KO) mouse lines using CRISPR/Cas9: single KO mice of Pate10 expressed in the caput epididymis; deletion KO mice of six caput epididymis-enriched genes (Pate5-7, 13, Gm27235, and Gm5916) (Pate7-Gm5916 KO); and deletion KO mice of four genes expressed in the placenta and epididymis (Pate8, 9, 11, and 12) (Pate8-12 KO). We observed that the fertility of only Pate7-Gm5916 KO males was reduced, whereas the rest remained unaffected. Furthermore, when the caput epididymis-enriched genes, Pate8 and Pate10 remained in Pate7-Gm5916 KO mice were independently deleted, both KO males displayed more severe subfertility due to a decrease in mature ADAM3 and a defect in sperm migration to the oviduct. Thus, our data showed that multiple caput epididymis-enriched genes within the region coding Pate5-13 cooperatively function to ensure male fertility in mice.
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http://dx.doi.org/10.1093/biolre/ioae008 | DOI Listing |
BMC Res Notes
September 2025
Center for Molecular Medicine Cologne, Faculty of Medicine, University Hospital Cologne, University of Cologne, Cologne, Germany.
Objectives: Small cell lung cancer (SCLC) accounts for approximately 15% of lung tumors and is marked by aggressive growth and early metastatic spread. In this study, we used two SCLC mouse models with differing tumor mutation burdens (TMB). To investigate tumor composition, spatial architecture, and interactions with the surrounding microenvironment, we acquired multiplexed images of mouse lung tumors using imaging mass cytometry (IMC).
View Article and Find Full Text PDFBreast Cancer Res
September 2025
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
Background: Polygenic risk scores (PRS) are not yet standard in clinical risk assessments for familial breast cancer in Sweden. This study evaluated the distribution and impact of an established PRS (PRS) in women undergoing clinical sequencing for hereditary breast cancer.
Findings: We integrated PRS into a hereditary breast cancer gene panel used in clinical practice and calculated scores for 262 women.
Nat Genet
September 2025
Department of Statistics, University of California, Berkeley, CA, USA.
The Ancestral Recombination Graph (ARG), which describes the genealogical history of a sample of genomes, is a vital tool in population genomics and biomedical research. Recent advancements have substantially increased ARG reconstruction scalability, but they rely on approximations that can reduce accuracy, especially under model misspecification. Moreover, they reconstruct only a single ARG topology and cannot quantify the considerable uncertainty associated with ARG inferences.
View Article and Find Full Text PDFNat Genet
September 2025
Department of Neurology, School of Medicine, University of California, Davis, Sacramento, CA, USA.
To understand shared and ancestry-specific genetic control of brain protein expression and its ramifications for disease, we mapped protein quantitative trait loci (pQTLs) in 1,362 brain proteomes from African American, Hispanic/Latin American and non-Hispanic white donors. Among the pQTLs that multiancestry fine-mapping MESuSiE confidently assigned as putative causal pQTLs in a specific population, most were shared across the three studied populations and are referred to as multiancestry causal pQTLs. These multiancestry causal pQTLs were enriched for exonic and promoter regions.
View Article and Find Full Text PDFJ Hum Genet
September 2025
Center for Medical Genetics, Keio University School of Medicine, Tokyo, Japan.
In standard short-read whole-exome sequencing (WES), capture probes are typically designed to target the protein-coding regions (CDS), and regions outside the exons-except for adjacent intronic sequences-are rarely sequenced. Although the majority of known pathogenic variants reside within the CDS as nonsynonymous variants, some disease-causing variants are located in regions that are difficult to detect by WES alone, such as deep intronic variants and structural variants, often requiring whole-genome sequencing (WGS) for detection. Moreover, WES has limitations in reliably identifying pathogenic variants within mitochondrial DNA or repetitive regions.
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