4.0 Article

A p57 conditional mutant allele that allows tracking of p57-expressing cells

Journal

GENESIS
Volume 55, Issue 4, Pages -

Publisher

WILEY
DOI: 10.1002/dvg.23025

Keywords

Cell cycle exit; CDKIs; Cre-inducible ablation; beta-galactosidase reporter; postnatal survival

Funding

  1. INSERM Avenir Program
  2. Association Francaise contre les Myopathies (AFM) via TRANSLAMUSCLE [PROJECT 19507]
  3. Labex REVIV [ANR-10-LABX-73]
  4. Fondation pour la Recherche Medicale (FRM) [FDT20130928236, DEQ20130326526]
  5. Agence Nationale pour la Recherche (ANR) grant Epimuscle [ANR 11 BSV2 017 02]
  6. Bone-muscle-repair [ANR-13BSV1-0011-02]
  7. BMP-biomass [ANR-12-BSV1-0038-04]
  8. Satnet [ANR-15-CE13-0011-01]
  9. RHU CARMMA [ANR-15RHUS-0003]
  10. Agence Nationale pour la Recherche Maladies Rares (MRAR) [ANR-06-MRAR-32-01]
  11. German Research Society (DFG) [GK1631 MyoGrad, KFO192 (Sp1152/8-1)]

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p57(Kip2) (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 (p57(FL-ILZ/+)) by flanking the coding exons 2-3 by LoxP sites. To track p57-expressing or mutant cells, the p57(FL-ILZ) allele also contains an IRES-linked beta-galactosidase reporter inserted in the 3' UTR of the gene. Here, we show that the b-galactosidase reporter expression pattern recapitulates p57 tissue specificity during development and in postnatal mice. Furthermore, we crossed the p57(FL-ILZ/+) mice with PGK-Cre mice to generate p57(cKO-ILZ/+) animals with ubiquitous loss of p57. p57(cKO-ILZ/+) mice display developmental phenotypes analogous to previously described p57 knock-outs. Thus, p57(FL-ILZ/+) is a new genetic tool allowing expression and functional conditional analyses of p57.

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