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Programmed Cell Death 2-Like (Pdcd2l) Is Required for Mouse Embryonic Development

Lookup NU author(s): Dr Brendan Houston, Richard Burke, Professor Joris VeltmanORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Copyright © 2020 Houston et al. Globozoospermia is a rare form of male infertility where men produce round-headed sperm that are incapable of fertilizing an oocyte naturally. In a previous study where we undertook a whole exome screen to define novel genetic causes of globozoospermia, we identified homozygous mutations in the gene PDCD2L Two brothers carried a p.(Leu225Val) variant predicted to introduce a novel splice donor site, thus presenting PDCD2L as a potential regulator of male fertility. In this study, we generated a Pdcd2l knockout mouse to test its role in male fertility. Contrary to the phenotype predicted from its testis-enriched expression pattern, Pdcd2l null mice died during embryogenesis. Specifically, we identified that Pdcd2l is essential for post-implantation embryonic development. Pdcd2l-/- embryos were resorbed at embryonic days 12.5-17.5 and no knockout pups were born, while adult heterozygous Pdcd2l males had comparable fertility to wildtype males. To specifically investigate the role of PDCD2L in germ cells, we employed Drosophila melanogaster as a model system. Consistent with the mouse data, global knockdown of trus, the fly ortholog of PDCD2L, resulted in lethality in flies at the third instar larval stage. However, germ cell-specific knockdown with two germ cell drivers did not affect male fertility. Collectively, these data suggest that PDCD2L is not essential for male fertility. By contrast, our results demonstrate an evolutionarily conserved role of PDCD2L in development.

Publication metadata

Author(s): Houston BJ, Oud MS, Aguirre DM, Merriner DJ, O'Connor AE, Okutman O, Viville S, Burke R, Veltman JA, O'Bryan MK

Publication type: Article

Publication status: Published

Journal: G3 Genes|Genomes|Genetics

Year: 2020

Volume: 10

Issue: 12

Pages: 4449-4457

Print publication date: 01/12/2020

Online publication date: 01/12/2020

Acceptance date: 01/10/2020

Date deposited: 02/08/2021

ISSN (electronic): 2160-1836

Publisher: Genetics Society of America


DOI: 10.1534/g3.120.401714

PubMed id: 33055224


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