The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates
- Institut Curie, France
- Queen Mary University of London, United Kingdom
Abstract
Genomic imprinting refers to the mono-allelic and parent-specific expression of a subset of genes. While long recognized for their role in embryonic development, imprinted genes have recently emerged as important modulators of postnatal physiology, notably through hypothalamus-driven functions. Here, using mouse models of loss, gain and parental inversion of expression, we report that the paternally expressed Zdbf2 gene controls neonatal growth in mice, in a dose-sensitive but parent-of-origin-independent manner. We further found that Zdbf2-KO neonates failed to fully activate hypothalamic circuits that stimulate appetite, and suffered milk deprivation and diminished circulating Insulin Growth Factor 1 (IGF-1). Consequently, only half of Zdbf2-KO pups survived the first days after birth and those surviving were smaller. This study demonstrates that precise imprinted gene dosage is essential for vital physiological functions at the transition from intra- to extra-uterine life, here the adaptation to oral feeding and optimized body weight gain.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files.RNA-Seq data have been deposited in GEO under accession code GSE153265
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RNA-seq of whole hypothalamus in WT and Zdbf2-KO neonatesNCBI Gene Expression Omnibus, GSE153265.
Article and author information
Author details
Funding
FP7 Ideas: European Research Council (ERC-Cog EpiRepro)
- Aurélie Teissandier
- Deborah Bourc'his
Fondation Bettencourt Schueller
- Deborah Bourc'his
Ligue Contre le Cancer
- Juliane Glaser
BTL Charity (GN417/2238)
- Angelica Gualtieri
- Carles Gaston-Massuet
Action Medical Research (GN2272)
- Angelica Gualtieri
- Carles Gaston-Massuet
DIM Biotherapies
- Juliane Glaser
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Joshua M Brickman, University of Copenhagen, Denmark
Ethics
Animal experimentation: All experimentation was approved by the Animal Care and Use Committee of the Institut Curie (agreement number: C 75-05-18) and adhered to European and National Regulation for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Directive 86/609 and 2010/63)
Version history
- Received: December 10, 2020
- Preprint posted: January 30, 2021 (view preprint)
- Accepted: January 19, 2022
- Accepted Manuscript published: January 20, 2022 (version 1)
- Version of Record published: February 2, 2022 (version 2)
Copyright
© 2022, Glaser 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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The imprinted Zdbf2 gene finely tunes control of feeding and growth in neonates
eLife 11:e65641.
https://doi.org/10.7554/eLife.65641
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