Dataset Information

The Prion-like protein Shadoo is involved in mouse embryonic and mammary development and differentiation.

ABSTRACT: Shadoo belongs to the prion protein family, an evolutionary conserved and extensively studied family due to the implication of PrP in Transmissible Spongiform Encephalopathies. However, the biological function of these genes remains poorly understood. While Sprn-knockdown experiments suggested an involvement of Shadoo during mouse embryonic development, Sprn-knockout experiments in 129Pas/C57BL/6J or 129Pas/FVB/NCr mice did not confirm it. In the present study, we analyzed the impact of Sprn gene invalidation in a pure FVB/NJ genetic background, using a zinc finger nuclease approach. The in-depth analysis of the derived knockout transgenic mice revealed a significant increase in embryonic lethality at early post-implantation stages, a growth retardation of young Sprn-knockout pups fed by wild type mice and a lactation defect of Sprn-knockout females. Histological and transcriptional analyses of knockout E7.5 embryos, E14.5 placentas and G7.5 mammary glands revealed specific roles of the Shadoo protein in mouse early embryogenesis, tissue development and differentiation with a potential antagonist action between PrP and Shadoo. This study thus highlights the entanglement between the proteins of the prion family.

SUBMITTER: Passet B

PROVIDER: S-EPMC7174383 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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The Prion-like protein Shadoo is involved in mouse embryonic and mammary development and differentiation.

Passet Bruno B Castille Johan J Makhzami Samira S Truchet Sandrine S Vaiman Anne A Floriot Sandrine S Moazami-Goudarzi Katayoun K Vilotte Marthe M Gaillard Anne-Laure AL Helary Louise L Bertaud Maud M Andréoletti Olivier O Vaiman Daniel D Calvel Pierre P Daniel-Carlier Nathalie N Moudjou Mohammed M Beauvallet Christian C Benharouga Mohamed M Laloé Denis D Mouillet-Richard Sophie S Duchesne Amandine A Béringue Vincent V Vilotte Jean-Luc JL

Scientific reports 20200421 1

Shadoo belongs to the prion protein family, an evolutionary conserved and extensively studied family due to the implication of PrP in Transmissible Spongiform Encephalopathies. However, the biological function of these genes remains poorly understood. While Sprn-knockdown experiments suggested an involvement of Shadoo during mouse embryonic development, Sprn-knockout experiments in 129Pas/C57BL/6J or 129Pas/FVB/NCr mice did not confirm it. In the present study, we analyzed the impact of Sprn gen ...[more]

PMID: 32317725

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Project description:BackgroundUnlike other tissues, development and differentiation of the mammary gland occur mostly after birth. The roles of systemic hormones and local growth factors important for this development and functional differentiation are well-studied. In other tissues, it has been shown that chromatin organization plays a key role in transcriptional regulation and underlies epigenetic regulation during development and differentiation. However, the role of chromatin organization in mammary gland development and differentiation is less well-defined. Here, we have studied the changes in chromatin organization at the milk protein gene loci (casein, whey acidic protein, and others) in the mouse mammary gland before and after functional differentiation.Methodology/principal findingsDistal regulatory elements within the casein gene cluster and whey acidic protein gene region have an open chromatin organization after pubertal development, while proximal promoters only gain open-chromatin marks during pregnancy in conjunction with the major induction of their expression. In contrast, other milk protein genes, such as alpha-lactalbumin, already have an open chromatin organization in the mature virgin gland. Changes in chromatin organization in the casein gene cluster region that are present after puberty persisted after lactation has ceased, while the changes which occurred during pregnancy at the gene promoters were not maintained. In general, mammary gland expressed genes and their regulatory elements exhibit developmental stage- and tissue-specific chromatin organization.Conclusions/significanceA progressive gain of epigenetic marks indicative of open/active chromatin on genes marking functional differentiation accompanies the development of the mammary gland. These results support a model in which a chromatin organization is established during pubertal development that is then poised to respond to the systemic hormonal signals of pregnancy and lactation to achieve the full functional capacity of the mammary gland.

Dataset Information

The Prion-like protein Shadoo is involved in mouse embryonic and mammary development and differentiation.

Publications

The Prion-like protein Shadoo is involved in mouse embryonic and mammary development and differentiation.

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