PMID- 35850260
OWN - NLM
STAT- MEDLINE
DCOM- 20231117
LR  - 20231117
IS  - 1095-564X (Electronic)
IS  - 0012-1606 (Linking)
VI  - 490
DP  - 2022 Oct
TI  - DDB1- and CUL4-associated factor 12-like protein 1 (Dcaf12l1) is not essential 
      for male fertility in mice.
PG  - 66-72
LID - S0012-1606(22)00139-7 [pii]
LID - 10.1016/j.ydbio.2022.07.006 [doi]
AB  - 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.
CI  - Copyright (c) 2022 Elsevier Inc. All rights reserved.
FAU - Houston, Brendan J
AU  - Houston BJ
AD  - School of BioSciences and Bio21 Institute, The University of Melbourne, 
      Parkville, VIC, Australia. Electronic address: brendan.houston@unimelb.edu.au.
FAU - Lopes, Alexandra M
AU  - Lopes AM
AD  - Instituto de Investigacao e Inovacao em Saude, Porto, Portugal; Instituto de 
      Patologia e Imunologia Molecular da Universidade do Porto, Portugal; Genetics of 
      Male Infertility Initiative (GEMINI), USA.
FAU - Laan, Maris
AU  - Laan M
AD  - Genetics of Male Infertility Initiative (GEMINI), USA; Faculty of Medicine, 
      Institute of Biomedicine and Translational Medicine, University of Tartu, 
      Estonia.
FAU - Nagirnaja, Liina
AU  - Nagirnaja L
AD  - Genetics of Male Infertility Initiative (GEMINI), USA; Division of Genetics, 
      Oregon National Primate Research Center, Beaverton, OR, USA.
FAU - O'Connor, Anne E
AU  - O'Connor AE
AD  - School of BioSciences and Bio21 Institute, The University of Melbourne, 
      Parkville, VIC, Australia.
FAU - Merriner, D Jo
AU  - Merriner DJ
AD  - School of BioSciences and Bio21 Institute, The University of Melbourne, 
      Parkville, VIC, Australia.
FAU - Nguyen, Joseph
AU  - Nguyen J
AD  - School of BioSciences and Bio21 Institute, The University of Melbourne, 
      Parkville, VIC, Australia.
FAU - Punab, Margus
AU  - Punab M
AD  - Genetics of Male Infertility Initiative (GEMINI), USA; Faculty of Medicine, 
      Institute of Biomedicine and Translational Medicine, University of Tartu, 
      Estonia; Andrology Centre, Tartu University Hospital, Tartu, Estonia; Faculty of 
      Medicine, Institute of Clinical Medicine, University of Tartu, Tartu, Estonia.
FAU - Riera-Escamilla, Antoni
AU  - Riera-Escamilla A
AD  - Andrology Department, Fundacio Puigvert, Universitat Autonoma de Barcelona, 
      Instituto de Investigaciones Biomedicas Sant Pau (IIB-Sant Pau), Barcelona, 
      Catalonia, Spain.
FAU - Krausz, Csilla
AU  - Krausz C
AD  - Genetics of Male Infertility Initiative (GEMINI), USA; International Male 
      Infertility Genomics Consortium (IMIGC); Department of Experimental and Clinical 
      Biomedical Sciences "Mario Serio", Centre of Excellence DeNothe, University of 
      Florence, Florence, Italy.
FAU - Aston, Kenneth Ivan
AU  - Aston KI
AD  - Genetics of Male Infertility Initiative (GEMINI), USA; International Male 
      Infertility Genomics Consortium (IMIGC); Division of Reproductive Endocrinology 
      and Infertility, School of Medicine, Washington University, St Louis, MO, USA.
FAU - Conrad, Donald F
AU  - Conrad DF
AD  - Genetics of Male Infertility Initiative (GEMINI), USA; Division of Genetics, 
      Oregon National Primate Research Center, Beaverton, OR, USA; International Male 
      Infertility Genomics Consortium (IMIGC).
FAU - O'Bryan, Moira K
AU  - O'Bryan MK
AD  - School of BioSciences and Bio21 Institute, The University of Melbourne, 
      Parkville, VIC, Australia; Genetics of Male Infertility Initiative (GEMINI), USA; 
      International Male Infertility Genomics Consortium (IMIGC).
LA  - eng
GR  - R01 HD078641/HD/NICHD NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20220715
PL  - United States
TA  - Dev Biol
JT  - Developmental biology
JID - 0372762
RN  - 9001-30-3 (Factor XII)
RN  - 0 (Dcaf12l1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Male
MH  - Mice
MH  - Factor XII/metabolism
MH  - *Fertility/genetics
MH  - *Infertility, Male/genetics
MH  - Mice, Knockout
MH  - Sperm Motility/genetics
MH  - Spermatogenesis/genetics
MH  - *Testis
OTO - NOTNLM
OT  - Azoospermia
OT  - DCAF12L1
OT  - Male infertility
OT  - Whole exome sequencing
EDAT- 2022/07/20 06:00
MHDA- 2022/09/14 06:00
CRDT- 2022/07/19 07:25
PHST- 2022/03/09 00:00 [received]
PHST- 2022/07/08 00:00 [revised]
PHST- 2022/07/11 00:00 [accepted]
PHST- 2022/07/20 06:00 [pubmed]
PHST- 2022/09/14 06:00 [medline]
PHST- 2022/07/19 07:25 [entrez]
AID - S0012-1606(22)00139-7 [pii]
AID - 10.1016/j.ydbio.2022.07.006 [doi]
PST - ppublish
SO  - Dev Biol. 2022 Oct;490:66-72. doi: 10.1016/j.ydbio.2022.07.006. Epub 2022 Jul 15.