@article{2cedd7ae0daa459c81e0d131a85d84eb,
title = "DDB1- and CUL4-associated factor 12-like protein 1 (Dcaf12l1) is not essential for male fertility in mice",
abstract = "Male infertility is a common condition affecting at least 7% of men worldwide and is often genetic in origin. Using whole exome sequencing, we recently discovered three hemizygous, likely damaging variants in DDB1- and CUL4-associated factor 12-like protein 1 (DCAF12L1) in men with azoospermia. DCAF12L1 is located on the X-chromosome and as identified by single cell sequencing studies, its expression is enriched in human testes and specifically in Sertoli cells and spermatogonia. However, very little is known about the role of DCAF12L1 in spermatogenesis, thus we generated a knockout mouse model to further explore the role of DCAF12L1 in male fertility. Knockout mice were generated using CRISPR/Cas9 technology to remove the entire coding region of Dcaf12l1 and were assessed for fertility over a broad range of ages (2–8 months of age). Despite outstanding genetic evidence in men, loss of DCAF12L1 had no discernible impact on male fertility in mice, as highlighted by breeding trials, histological assessment of the testis and epididymis, daily sperm production and evaluation of sperm motility using computer assisted methods. This disparity is likely due to the parallel evolution, and subsequent divergence, of DCAF12 family members in mice and men or the presence of compounding environmental factors in men.",
keywords = "Azoospermia, DCAF12L1, Male infertility, Whole exome sequencing",
author = "Houston, {Brendan J.} and Lopes, {Alexandra M.} and Maris Laan and Liina Nagirnaja and O'Connor, {Anne E.} and Merriner, {D. Jo} and Joseph Nguyen and Margus Punab and Antoni Riera-Escamilla and Csilla Krausz and Aston, {Kenneth Ivan} and Conrad, {Donald F.} and O'Bryan, {Moira K.}",
note = "Funding Information: Australian National Health and Medical Research grant to MKOB, KIA and DFC (APP1120356).US National Institutes of Health grant to DFC (R01HD078641).Estonia Research Council grant to ML and MP (PRG1021).Portuguese Government Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia (IF/01262/2014) to AML.The IPATIMUP i3S Research Unit is partially supported by Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia project Institute for Research and Innovation in Health Sciences” (POCI-01-0145-FEDER-007274).We thank Dr. Christen Mirth and Dr. Andr{\'e} Nogueira Alves for their assistance with the statistical analyses. Phenomics Australia is supported by the Australian Government Department of Education through the National Collaborative Research Infrastructure Strategy, the Super Science Initiative, and the Collaborative Research Infrastructure Scheme. Funding Information: Estonia Research Council grant to ML and MP ( PRG1021 ). Funding Information: The IPATIMUP i3S Research Unit is partially supported by Funda{\c c}{\~a}o para a Ci{\^e}ncia e Tecnologia project Institute for Research and Innovation in Health Sciences ” ( POCI-01-0145-FEDER-007274 ). Funding Information: We thank Dr. Christen Mirth and Dr. Andr{\'e} Nogueira Alves for their assistance with the statistical analyses. Phenomics Australia is supported by the Australian Government Department of Education through the National Collaborative Research Infrastructure Strategy, the Super Science Initiative, and the Collaborative Research Infrastructure Scheme. Publisher Copyright: {\textcopyright} 2022 Elsevier Inc.",
year = "2022",
month = oct,
doi = "10.1016/j.ydbio.2022.07.006",
language = "English (US)",
volume = "490",
pages = "66--72",
journal = "Developmental Biology",
issn = "0012-1606",
publisher = "Academic Press Inc.",
}