Over-expression of an endogenous milk protein gene in transgenic mice is associated with impaired mammary alveolar development and a milchlos phenotype

Tom Burdon, Robert J Wall, Avi Shamay, Gilbert H. Smith, Lothar Hennighausen

Research output: Contribution to journalArticlepeer-review

Abstract

The whey acidic protein (WAP) gene is expressed in mammary epithelial cells at late pregnancy and throughout lactation. We have generated transgenic mice in which a mouse WAP transgene is expressed precociously in pregnancy. From 13 founder mice bearing WAP transgenes, two female founders and the daughters from a male founder failed to lactate and nurture their offspring. We named this phenotype milchlos. Mammary tissue from postpartum milchlos mice was underdeveloped, contained too few alveoli and resembled the glands of non-transgenic mid-pregnant mice. The hypothesis that alveolar development in milchlos mice was functionally arrested in a prelactational state is consistent with low levels of alpha-lactalbumin mRNA, and an unidentified keratin RNA in mammary tissue from postpartum mice. Defects in alveolar function in milchlos mice were detected at mid-pregnancy; in non-transgenic mice, WAP was secreted into the alveolar lumen but remained preferentially in the cytoplasm of the alveolar epithelial cells in the milchlos mice. Since deregulated WAP expression resulted in impaired mammary development, it is possible that WAP plays a regulatory role in the terminal differentiation and development of mammary alveolar cells.
Original languageEnglish
Pages (from-to)67-74
Number of pages8
JournalMechanisms of Development
Volume36
Issue number1-2
DOIs
Publication statusPublished - Dec 1991

Keywords

  • Animals
  • Cell Differentiation
  • Female
  • Gene Expression Regulation, Bacterial
  • Male
  • Mammary Glands, Animal/pathology
  • Mice
  • Mice, Transgenic
  • Milk Proteins/genetics
  • Pedigree
  • Phenotype
  • Pregnancy

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