CRISPR/Cas9-mediated genome editing reveals 30 testis-enriched genes dispensable for male fertility in mice†.
CRISPR/Cas9
knockout mice
male infertility
spermatogenesis
testis expression
Journal
Biology of reproduction
ISSN: 1529-7268
Titre abrégé: Biol Reprod
Pays: United States
ID NLM: 0207224
Informations de publication
Date de publication:
01 08 2019
01 08 2019
Historique:
accepted:
07
06
2019
received:
17
05
2019
pubmed:
16
6
2019
medline:
30
9
2020
entrez:
16
6
2019
Statut:
ppublish
Résumé
More than 1000 genes are predicted to be predominantly expressed in mouse testis, yet many of them remain unstudied in terms of their roles in spermatogenesis and sperm function and their essentiality in male reproduction. Since individually indispensable factors can provide important implications for the diagnosis of genetically related idiopathic male infertility and may serve as candidate targets for the development of nonhormonal male contraceptives, our laboratories continuously analyze the functions of testis-enriched genes in vivo by generating knockout mouse lines using the CRISPR/Cas9 system. The dispensability of genes in male reproduction is easily determined by examining the fecundity of knockout males. During our large-scale screening of essential factors, we knocked out 30 genes that have a strong bias of expression in the testis and are mostly conserved in mammalian species including human. Fertility tests reveal that the mutant males exhibited normal fecundity, suggesting these genes are individually dispensable for male reproduction. Since such functionally redundant genes are of diminished biological and clinical significance, we believe that it is crucial to disseminate this list of genes, along with their phenotypic information, to the scientific community to avoid unnecessary expenditure of time and research funds and duplication of efforts by other laboratories.
Identifiants
pubmed: 31201419
pii: 5519226
doi: 10.1093/biolre/ioz103
pmc: PMC6735960
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
501-511Subventions
Organisme : NICHD NIH HHS
ID : P01 HD087157
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD088412
Pays : United States
Organisme : NICHD NIH HHS
ID : R01 HD095341
Pays : United States
Informations de copyright
© The Author(s) 2019. Published by Oxford University Press on behalf of Society for the Study of Reproduction.
Références
J Mol Biol. 2001 Jan 19;305(3):567-80
pubmed: 11152613
Proc Natl Acad Sci U S A. 2003 Oct 14;100(21):12201-6
pubmed: 14526100
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14864-8
pubmed: 14657352
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14869-74
pubmed: 14657366
Nature. 2005 Mar 10;434(7030):234-8
pubmed: 15759005
J Biol Chem. 2006 Mar 3;281(9):5634-9
pubmed: 16407235
Proc Natl Acad Sci U S A. 2006 Mar 28;103(13):4982-7
pubmed: 16549803
Proc Natl Acad Sci U S A. 2007 Jan 23;104(4):1219-23
pubmed: 17227845
FEBS Lett. 2008 Apr 9;582(8):1203-9
pubmed: 18325338
Biol Reprod. 2009 Feb;80(2):358-66
pubmed: 18987332
Nat Med. 2008 Nov;14(11):1197-213
pubmed: 18989307
Mol Cells. 2009 Feb 28;27(2):199-203
pubmed: 19277502
Proc Natl Acad Sci U S A. 2009 Oct 6;106(40):17055-60
pubmed: 19805151
J Clin Invest. 2010 Apr;120(4):984-94
pubmed: 20364096
Nat Methods. 2011 Sep 29;8(10):785-6
pubmed: 21959131
Nature. 2012 Sep 6;489(7414):57-74
pubmed: 22955616
Sci Rep. 2013 Nov 27;3:3355
pubmed: 24284873
Mol Cell Proteomics. 2014 Feb;13(2):397-406
pubmed: 24309898
Asian J Androl. 2015 Jan-Feb;17(1):86-93
pubmed: 25248657
Bioinformatics. 2015 Apr 1;31(7):1120-3
pubmed: 25414360
Reproduction. 2015 Nov;150(5):R159-74
pubmed: 26447148
Mol Hum Reprod. 2016 Feb;22(2):69-82
pubmed: 26612782
Proc Natl Acad Sci U S A. 2016 Jul 12;113(28):7704-10
pubmed: 27357688
Lancet Diabetes Endocrinol. 2017 Jul;5(7):544-553
pubmed: 27395771
Sci Rep. 2016 Aug 17;6:31666
pubmed: 27530713
FEBS Lett. 2016 Oct;590(20):3526-3537
pubmed: 27670266
Development. 2017 Feb 15;144(4):624-634
pubmed: 28087628
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5370-E5378
pubmed: 28630322
Methods Mol Biol. 2017;1630:67-80
pubmed: 28643250
Cell Stem Cell. 2017 Oct 5;21(4):533-546.e6
pubmed: 28985528
Nucleic Acids Res. 2018 Jan 4;46(D1):D754-D761
pubmed: 29155950
Nat Rev Urol. 2018 May;15(5):287-307
pubmed: 29532805
Nat Rev Urol. 2018 Jun;15(6):369-384
pubmed: 29622783
Nat Rev Urol. 2018 Sep;15(9):535-562
pubmed: 29967387
J Cell Sci. 2018 Oct 11;131(19):
pubmed: 30185526
Nucleic Acids Res. 2019 Jan 8;47(D1):D807-D811
pubmed: 30395283
Nature. 2019 Apr;568(7751):259-263
pubmed: 30944473
Nature. 2019 Apr;568(7751):193-197
pubmed: 30944477
J Biol Chem. 1994 Dec 16;269(50):31845-9
pubmed: 7989357
Development. 1997 Oct;124(20):4121-31
pubmed: 9374408
Bioinformatics. 1998;14(4):378-9
pubmed: 9632836