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

Bruno B. Passet (1) , Johan Castille (1) , Samira Makhzami (1) , Sandrine Truchet (2) , Anne Vaiman (1) , Sandrine Floriot (1) , Katayoun Moazami-Goudarzi (1) , Marthe Vilotte (1) , Anne-Laure Gaillard (1) , Louise Hélary (1) , Maud Bertaud (1) , Olivier Andreoletti (3) , Daniel Vaiman (4) , Pierre Calvel (1) , Nathalie Daniel-Carlier (1) , Mohammed Moudjou (2) , Christian Beauvallet (1) , Mohamed Benharouga (5) , Denis Laloë (1) , Sophie Mouillet-Richard (6) , Amandine Duchesne (1) , Vincent Béringue (2) , Jean-Luc Vilotte (1)

1 GABI - Génétique Animale et Biologie Intégrative
2 VIM (UR 0892) - Virologie et Immunologie Moléculaires
3 IHAP - Interactions hôtes-agents pathogènes [Toulouse]
4 IC UM3 (UMR 8104 / U1016) - Institut Cochin
5 BioMet - Biologie des Métaux
6 CRC (UMR_S_1138 / U1138) - Centre de Recherche des Cordeliers

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.

Domains: Life Sciences [q-bio]; Development Biology

Bruno B. Passet, Johan Castille, Samira Makhzami, Sandrine Truchet, Anne Vaiman, et al.. The Prion-like protein Shadoo is involved in mouse embryonic and mammary development and differentiation. Scientific Reports, 2020, 10 (1), pp.6765. ⟨10.1038/s41598-020-63805-y⟩. ⟨hal-02556266⟩