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Evaluation of Mammary Gland Development and Function in Mouse Models
08:51

Evaluation of Mammary Gland Development and Function in Mouse Models

Published on: July 21, 2011

ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation

F E Jones1, T Welte, X Y Fu

  • 1Department of Pathology, BML 342, Yale University School of Medicine, New Haven, Connecticut 06520-8023, USA.

The Journal of Cell Biology
|October 6, 1999
PubMed

Insights

Epidermal growth factor receptor ErbB4 signaling is crucial for mammary gland terminal differentiation. Inactivation of ErbB4 signaling disrupts lactation and Stat5 activation during mid-lactation in mice.

Area of Science:

  • Cellular biology
  • Developmental biology
  • Molecular biology

Background:

  • Epidermal growth factor receptor (EGFR) family signaling is vital for breast development and cancer.
  • ErbB4, a member of the EGFR family, has unique roles in mammary tissue.
  • Previous research indicated distinct responses mediated by ErbB4 in the mammary gland.

Purpose of the Study:

  • To investigate the function of ErbB4 signaling in normal mouse mammary gland development.
  • To understand the specific role of ErbB4 in mammary gland differentiation and lactation.

Main Methods:

  • Generated a transgenic mouse model expressing a dominant-negative ErbB4 allele (ErbB4DeltaIC).
  • Analyzed mammary gland phenotype at mid-lactation (12-d postpartum).
  • Assessed gene expression (beta-casein, whey acidic protein, alpha-lactalbumin) using in situ hybridization and protein activation (Stat5 phosphorylation) via immunohistochemistry.

Main Results:

  • ErbB4 inactivation did not cause a phenotype until mid-lactation.
  • Mammary lobuloalveoli expressing ErbB4DeltaIC showed condensation and lacked luminal lactation products.
  • While beta-casein mRNA levels were normal, whey acidic protein mRNA was reduced, and alpha-lactalbumin mRNA was undetectable.
  • Stat5 was expressed but not phosphorylated (inactive) in ErbB4DeltaIC-expressing tissue.
  • ErbB4 induced Stat5 phosphorylation in transiently expressed 293T cells, dependent on the Stat5 SH2 domain.

Conclusions:

  • ErbB4 signaling is essential for mammary gland terminal differentiation.
  • ErbB4 activation is necessary for Stat5 activation at mid-lactation.
  • Disruption of ErbB4 signaling impairs lactation by affecting differentiation and Stat5 signaling pathways.

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