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INRA
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Dernière mise à jour : Mai 2018

Menu Logo Principal AgroParisTech Université Paris-Saclay

INRA GABI Unit

GABI : Génétique Animale et Biologie IntégrativeUnité Mixte de Recherche INRA - AgroParisTech

Dnajc2, a new actor necessary for the early development of mammal embryos

Dnajc2
The in vivo function of the Dnajc2 gene during development is poorly known. Cell culture experiments have suggested that the DNAJC2 protein could play a favorable role on muscle development (Alwan et al., 2017). Therefore, this gene could be a lever for selection on meat production and a candidate gene for certain human muscle anomalies. The analysis of its role in vivo was perfomed by invalidating this locus using gene editing on mice.

MOTS-CLES : Dnajc2, preimplantation development, maternal RNA, genome editing

5150-1536
The functions currently described for the DNAJC2 protein concern transcription and epigenesis. Invalidation of Dnajc2 i) in vivo using Crispr/Cas9 in mice and ii) in vitro by injecting interfering RNA in oocytes in culture showed that DNAJC2 is one of those rare proteins currently described as being necessary to embryo development and present at the earliest stages of development due to maternal heritability.

 

The in vivo function of the Dnajc2 gene during development is poorly known. Cell culture experiments have suggested that the DNAJC2 protein could play a favorable role on muscle development  (Alwan et al., 2017). Therefore, this gene could be a lever for selection on meat production and a candidate gene for certain human muscle anomalies. The analysis of its role in vivo was perfomed by invalidating this locus using gene editing on mice.  

Invalidation of Dnajc2 gene was done using CRISPR/Cas9 technology on FVB/NJ mice. Two mouse lines were obtained. No invalidated baby mice were observed in the descendants nor between heterozygous mice. Such embryos were detected by analyses during gestation up to implantation. Beyond this stage, embryos invalidated for Dnajc2 are no longer present and the empty deciduae were observed, indicating that their implantation occurred just before their lysis.

The anlaysis of preimplantation embryos showed that they all expressed the DNAJC2 protein, independently of their genetic status, suggesting the presence of RNA coding for this protein in the oocyte, probably of maternal origin. To support this hypothesis, invalidating these RNA was done by injecting interfering RNA. Following this injection, these oocytes were not able to develop in vitro up to the blastocyst stage, validating the role of maternal RNA.

In conclusion, Dnajc2 is a gene whose invalidation is responsible for an early embryo lethality and whose transcript is present in germ cells.

The main role of Dnajc2 gene on early embryo development in mammals makes it a candidate to explain the following : 1) reproductive defects observed in certain crosses between farm animals. The search for mutations in this locus could be unertaken using data collected notably on some bovine breeds for cows presenting an abnormally high rate of return to heat to support this hypothesis ; ii) reprodution difficulties for some couples.

Contact(s)

Scientific Contact(s):

Associated Division(s): Animal Genetics

Associated Center(s): Jouy-en-josas

 

#3Perf

INRAE priority in their Guidance Document

#3Perf-2: Using biology and technology techniques for multiperformance.

See also

Bibliography

Helary L, Castille J, Passet B, Vaiman A, Beauvallet C, Jaffrezic F, Charles M, Tamzini M, Baraige F, Letheule M, Laubier J, Moazami-Goudarzi K, Vilotte JL, Blanquet V, Duchesne A. DNAJC2 is required for mouse early embryonic development. Biochem Biophys Res Commun. 2019 Aug 13;516(1):258-263. doi: 10.1016/j.bbrc.2019.06.009. Epub 2019 Jun 21.