DDB1- and CUL4-associated factor 12-like protein 1 (Dcaf12l1) is not essential for male fertility in mice

Brendan J. Houston, Alexandra M. Lopes, Maris Laan, Liina Nagirnaja, Anne E. O'Connor, D. Jo Merriner, Joseph Nguyen, Margus Punab, Antoni Riera-Escamilla, Csilla Krausz, Kenneth Ivan Aston, Donald F. Conrad, Moira K. O'Bryan

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish (US)
Pages (from-to)66-72
Number of pages7
JournalDevelopmental Biology
StatePublished - Oct 2022


  • Azoospermia
  • DCAF12L1
  • Male infertility
  • Whole exome sequencing

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


Dive into the research topics of 'DDB1- and CUL4-associated factor 12-like protein 1 (Dcaf12l1) is not essential for male fertility in mice'. Together they form a unique fingerprint.

Cite this