title: A p57 conditional mutant allele that allows tracking of p57-expressing cells.
abstract: p57Kip2(p57) is a maternally expressed imprinted gene regulating growth arrest which belongs to the CIP/KIP family of cyclin-dependent kinase inhibitors. While initially identified as a cell cycle arrest protein through inhibition of cyclin and cyclin-dependent kinase complexes, p57 activity has also been linked to differentiation, apoptosis, and senescence. In addition, p57 has recently been shown to be involved in tumorigenesis and cell fate decisions in stem cells. Yet, p57 function in adult tissues remains poorly characterized due to the perinatal lethality of p57 knock-out mice. To analyze p57 tissue-specific activity, we generated a conditional mouse line (p57FL-ILZ/+) by flanking the coding exons 2-3 by LoxP sites. To track p57-expressing or mutant cells, the p57FL-ILZallele also contains an IRES-linked β-galactosidase reporter inserted in the 3' UTR of the gene. Here, we show that the β-galactosidase reporter expression pattern recapitulates p57 tissue specificity during development and in postnatal mice. Furthermore, we crossed the p57FL-ILZ/+mice with PGK-Cre mice to generate p57cKO-ILZ/+animals with ubiquitous loss of p57. p57cKO-ILZ/+mice display developmental phenotypes analogous to previously described p57 knock-outs. Thus, p57FL-ILZ/+is a new genetic tool allowing expression and functional conditional analyses of p57.
authors.affiliation: Inserm, IMRB U955-E10, Creteil, F-94010, France.|Université Paris Est, Faculté de medecine, F-94000, Creteil, & Ecole Nationale Veterinaire d'Alfort, Maison Alfort, 94700, France.
authors.forename: Despoina
authors.identifier: 0000-0002-4494-7234
authors.initials: D
authors.lastname: Mademtzoglou
authors.affiliation: Inserm, IMRB U955-E10, Creteil, F-94010, France.|Université Paris Est, Faculté de medecine, F-94000, Creteil, & Ecole Nationale Veterinaire d'Alfort, Maison Alfort, 94700, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Alonso-Martin
authors.affiliation: Inserm, IMRB U955-E10, Creteil, F-94010, France.|Université Paris Est, Faculté de medecine, F-94000, Creteil, & Ecole Nationale Veterinaire d'Alfort, Maison Alfort, 94700, France.
authors.forename: Ted Hung-Tse
authors.initials: TH
authors.lastname: Chang
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, Center for Research in Myology, Paris, France.
authors.forename: Keren
authors.initials: K
authors.lastname: Bismuth
authors.affiliation: Inserm, IMRB U955-E10, Creteil, F-94010, France.|Université Paris Est, Faculté de medecine, F-94000, Creteil, & Ecole Nationale Veterinaire d'Alfort, Maison Alfort, 94700, France.
authors.forename: Bernadette
authors.initials: B
authors.lastname: Drayton-Libotte
authors.affiliation: Inserm, IMRB U955-E10, Creteil, F-94010, France.|Université Paris Est, Faculté de medecine, F-94000, Creteil, & Ecole Nationale Veterinaire d'Alfort, Maison Alfort, 94700, France.|Sorbonne Universités, UPMC Univ Paris 06, INSERM UMRS974, Center for Research in Myology, Paris, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Aurade
authors.affiliation: Inserm, IMRB U955-E10, Creteil, F-94010, France.|Université Paris Est, Faculté de medecine, F-94000, Creteil, & Ecole Nationale Veterinaire d'Alfort, Maison Alfort, 94700, France.|Etablissement Français du Sang, Creteil, 94017, France.|DHU Pepsy & Centre de Référence des Maladies Neuromusculaires GNMH, APHP, Hopitaux Universitaires Henri Mondor, Creteil, 94000, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Relaix
mesh_terms: D000483:Alleles; D000818:Animals; D002478:Cells, Cultured; D050761:Cyclin-Dependent Kinase Inhibitor p57 / Q000235:genetics* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism; D005260:Female; D018390:Gene Targeting / Q000379:methods*; D017930:Genes, Reporter; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009928:Organ Specificity; D010641:Phenotype; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: C493965:Cdkn1c protein, mouse; D050761:Cyclin-Dependent Kinase Inhibitor p57; D001616:beta-Galactosidase
keywords: CDKIs; Cell cycle exit; Cre-inducible ablation; postnatal survival; β-galactosidase reporter