Evidence map›Paper›PMID 31009948›Full record

ArticleHuman molecular genetics2019

Targeted knock-in mice with a human mutation in GRTH/DDX25 reveals the essential role of phosphorylated GRTH in spermatid development during spermatogenesis.

Raghuveer Kavarthapu, Rajakumar Anbazhagan, Murugananthkumar Raju, Chon-Hwa Tsai Morris, James Pickel, Maria L Dufau

Open access · hybridAbstract read
In one paragraph

Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.1field-weighted citation impact, top 23% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

17 citing papers in PubMed, 19 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Article
  6. Article
  7. Article
  8. Comparative Ubiquitome Analysis Reveals Deubiquitinating Effects Induced byInternational journal of molecular sciences · 2022
    Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Raghuveer KavarthapuSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Rajakumar AnbazhaganSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Murugananthkumar RajuSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
Chon-Hwa Tsai MorrisSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
James PickelTransgenic Core, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
Maria L DufauSection on Molecular Endocrinology, Division of Developmental Biology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA.
National Institutes of Health · USEunice Kennedy Shriver National Institute of Child Health and Human Development · US

Funding

Transgenic Resources for Neuroscience ResearchZICMH002901 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI AMARA, SUSAN · 2009 to 2025
$36.5M
Regulation of Hormone Receptors and Gonadal GenesZIAHD000150 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI DUFAU, MARIA · 2009 to 2022
$15.9M
6 · The paper itself

Abstract

Gonadotropin-regulated testicular RNA helicase (GRTH/DDX25) is a testis specific member of the DEAD-box family of RNA helicases expressed in meiotic and haploid germ cells which plays an essential role in spermatogenesis. There are two species of GRTH the 56 kDa non-phospho and 61 kDa phospho forms. Our early studies revealed a missense mutation (R242H) of GRTH in azoospermic men that when expressed in COS1-cells lack the phospho-form of GRTH. To investigate the role of the phospho-GRTH species in spermatogenesis, we generated a GRTH knock-in (KI) transgenic mice with the R242H mutation. GRTH-KI mice are sterile with reduced testis size, lack sperm with spermatogenic arrest at round spermatid stage and loss of the cytoplasmic phospho-GRTH species. Electron microscopy studies revealed reduction in the size of chromatoid bodies (CB) of round spermatids (RS) and germ cell apoptosis. We observed absence of phospho-GRTH in the CB of RS. Complete loss of chromatin remodeling and related proteins such as TP2, PRM2, TSSK6 and marked reduction of their respective mRNAs and half-lives were observed in GRTH-KI mice. We showed that phospho-GRTH has a role in TP2 translation and revealed its occurrence in a 3' UTR dependent manner. These findings demonstrate the relevance of phospho-GRTH in the structure of the chromatoid body, spermatid development and completion of spermatogenesis and provide an avenue for the development of a male contraceptive.

Indexed as

Mutation, MissenseProtein Processing, Post-TranslationalAnimalsAspermiaChromatin Assembly and DisassemblyDEAD-box RNA HelicasesGene Expression RegulationInfertility, MaleMaleMiceMice, KnockoutPhosphorylationProtaminesProtein Serine-Threonine KinasesSpermatidsSpermatogenesisDDX25 protein, humanDdx25 protein, mouseDEAD-box RNA Helicasesprotamine 2ProtaminesProtein Serine-Threonine KinasesTssk6 protein, mouse

Identifiers

PMID31009948
PMCPMC6644162
OpenAlexW2941454621

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.