Inducible knockout of ∆Np63 alters cell polarity and metabolism during pubertal mammary gland development

FEBS Lett. 2020 Mar;594(6):973-985. doi: 10.1002/1873-3468.13703. Epub 2019 Dec 17.


The ∆Np63 isoform of the p53-family transcription factor Trp63 is a key regulator of mammary epithelial stem cells that is involved in breast cancer development. To investigate the role of ∆Np63 at different stages of normal mammary gland development, we generated a ∆Np63-inducible conditional knockout (cKO) mouse model. We demonstrate that the deletion of ∆Np63 at puberty results in depletion of mammary stem cell-enriched basal cells, reduces expression of E-cadherin and β-catenin, and leads to a closed ductal lumen. RNA-sequencing analysis reveals reduced expression of oxidative phosphorylation (OXPHOS)-associated proteins and desmosomal polarity proteins. Functional assays show reduced numbers of mitochondria in the mammary epithelial cells of ΔNp63 cKO compared to wild-type, supporting the reduced OXPHOS phenotype. These findings identify a novel role for ∆Np63 in cellular metabolism and mammary epithelial cell polarity.

Keywords: OXPHOS; mammary gland; polarity; stem cells; ∆Np63.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Polarity*
  • Female
  • Mammary Glands, Animal / metabolism*
  • Mice
  • Mice, Knockout
  • Sexual Maturation*
  • Stem Cells / metabolism*
  • Trans-Activators / genetics
  • Trans-Activators / metabolism*
  • beta Catenin / genetics
  • beta Catenin / metabolism


  • CTNNB1 protein, mouse
  • Cadherins
  • Cdh1 protein, mouse
  • Trans-Activators
  • Trp63 protein, mouse
  • beta Catenin