Deficient spermiogenesis in mice lacking Rlim

  1. Feng Wang
  2. Maria Gracia Gervasi
  3. Ana Bošković
  4. Fengyun Sun
  5. Vera D Rinaldi
  6. Jun Yu
  7. Mary C Wallingford
  8. Darya A Tourzani
  9. Jesse Mager
  10. Lihua J Zhu
  11. Oliver J Rando
  12. Pablo E Visconti
  13. Lara Strittmatter
  14. Ingolf Bach  Is a corresponding author
  1. University of Massachusetts Medical School, United States
  2. University of Massachusetts Amherst, United States

Abstract

The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile. Here we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene results in lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis.

Data availability

RNAseq data have been deposited in GEO under accession code GSE114593.

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Feng Wang

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Maria Gracia Gervasi

    Department of Veterinary and Animal Science, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Ana Bošković

    Biochemistry, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Fengyun Sun

    Department of Biochemistry, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Vera D Rinaldi

    Department of Biochemistry, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0051-1754
  6. Jun Yu

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Mary C Wallingford

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Darya A Tourzani

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  9. Jesse Mager

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Lihua J Zhu

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Oliver J Rando

    Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1516-9397
  12. Pablo E Visconti

    Dept of Veterinary & Animal Sciences, University of Massachusetts Amherst, Amherst, United States
    Competing interests
    The authors declare that no competing interests exist.
  13. Lara Strittmatter

    Electron microscopy core, University of Massachusetts Medical School, Worcester, United States
    Competing interests
    The authors declare that no competing interests exist.
  14. Ingolf Bach

    Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, United States
    For correspondence
    ingolf.bach@umassmed.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4505-8946

Funding

National Institutes of Health (GM128168)

  • Ingolf Bach

National Institutes of Health (HD080224)

  • Oliver J Rando

National Institutes of Health (HD38082)

  • Pablo E Visconti

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All mice were housed in the animal facility of UMMS and utilized according to NIH guidelines and those established by the UMMS Institute of Animal Care and Usage Committee (IACUC; protocol #201900344).

Reviewing Editor

  1. Jeannie T Lee, Massachusetts General Hospital, United States

Publication history

  1. Received: September 29, 2020
  2. Accepted: February 22, 2021
  3. Accepted Manuscript published: February 23, 2021 (version 1)
  4. Accepted Manuscript updated: February 24, 2021 (version 2)
  5. Version of Record published: March 5, 2021 (version 3)

Copyright

© 2021, Wang et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Feng Wang
  2. Maria Gracia Gervasi
  3. Ana Bošković
  4. Fengyun Sun
  5. Vera D Rinaldi
  6. Jun Yu
  7. Mary C Wallingford
  8. Darya A Tourzani
  9. Jesse Mager
  10. Lihua J Zhu
  11. Oliver J Rando
  12. Pablo E Visconti
  13. Lara Strittmatter
  14. Ingolf Bach
(2021)
Deficient spermiogenesis in mice lacking Rlim
eLife 10:e63556.
https://doi.org/10.7554/eLife.63556

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