Essential role of eIF5A-1 and deoxyhypusine synthase in mouse embryonic development
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Updated: May 30, 2026
Immunohistochemical Detection of 5-Methylcytosine and 5-Hydroxymethylcytosine in Developing and Postmitotic Mouse Retina
Published on: August 29, 2018
Kazuhiro Nishimura1, Seung Bum Lee, Jong Hwan Park
1Oral and Pharyngeal Cancer Branch, NIDCR, National Institutes of Health, Bethesda, MD 20892-4340, USA.
Insights
The eukaryotic initiation factor 5A (eIF5A) and deoxyhypusine synthase (DHPS) are essential for early mammalian development. Knocking out their genes in mice caused embryonic lethality, highlighting their vital roles.
Area of Science:
- Molecular Biology
- Developmental Biology
- Biochemistry
Background:
- Eukaryotic initiation factor 5A (eIF5A) is a protein containing a unique hypusine modification.
- Hypusine is derived from spermidine and is added by deoxyhypusine synthase (DHPS).
- The conservation of eIF5A and DHPS suggests critical cellular functions.
Purpose of the Study:
- To investigate the roles of eIF5A and DHPS in mammalian development.
- To determine the consequences of knocking out the Eif5a or Dhps genes in mice.
Main Methods:
- Gene knockout in mice to create Eif5a and Dhps heterozygous and homozygous models.
- Analysis of embryonic development and blastocyst growth in vitro.
Main Results:
- Homozygous Eif5a and Dhps knockout embryos exhibited lethality between E3.5 and E7.5.
- Homozygous Eif5a and Dhps blastocysts showed growth defects in vitro compared to controls.
- Heterozygous knockout mice were viable and fertile.
Conclusions:
- Both eIF5A-1 and DHPS are essential for early embryonic development in mammals.
- Disruption of eIF5A or DHPS function leads to embryonic lethality.
- These findings underscore the critical importance of the hypusine modification pathway in development.
Abstract:
The eukaryotic initiation factor 5A (eIF5A) contains a polyamine-derived amino acid, hypusine [N(ε)-(4-amino-2-hydroxybutyl)lysine]. Hypusine is formed post-translationally by the addition of the 4-aminobutyl moiety from the polyamine spermidine to a specific lysine residue, catalyzed by deoxyhypusine synthase (DHPS), and subsequent hydroxylation by deoxyhypusine hydroxylase (DOHH). The eIF5A precursor protein and both of its modifying enzymes are highly conserved, suggesting a vital cellular function for eIF5A and its hypusine modification. To address the functions of eIF5A and the first modification enzyme, DHPS, in mammalian development, we knocked out the Eif5a or the Dhps gene in mice. Eif5a heterozygous knockout mice and Dhps heterozygous knockout mice were viable and fertile. However, homozygous Eif5a1 (gt/gt) embryos and Dhps (gt/gt) embryos died early in embryonic development, between E3.5 and E7.5. Upon transfer to in vitro culture, homozygous Eif5a (gt/gt) or Dhps (gt/gt) blastocysts at E3.5 showed growth defects when compared to heterozygous or wild type blastocysts. Thus, the knockout of either the eIF5A-1 gene (Eif5a) or of the deoxyhypusine synthase gene (Dhps) caused early embryonic lethality in mice, indicating the essential nature of both eIF5A-1 and deoxyhypusine synthase in mammalian development.
