Transgenic mice carrying the guinea-pig α-lactalbumin gene transcribe milk protein genes in their sebaceous glands during lactation

A. Maschio, P. M. Brickell, D. Kioussis, A. L. Mellor, D. Katz, R. K. Craig

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

We have generated transgenic mice carrying the entire guinea-pig α-lactalbumin gene. Lactating transgenic mice expressed high levels of correctly initiated and processed guinea-pig α-lactalbumin mRNA in the secretory epithelium of their mammary glands, and secreted guinea-pig α-lactalbumin intheir milk. Transcripts were detectable after 7 days of pregnancy, indicating that the transgene was under correct hormonal control. Whereas no or negligible transcription was detectable in all other tissues tested, high levels of transcripts were found in the skin of lactating transgenic mice. Guinea-pig α-lactalbumin protein was undetectable in the skin, however. In situ hybridization analysis showed that expression was localized to the undifferentiated cells in the basal layer of the sebaceous glands. Further studies revealed high levels of endogenous β-casein mRNA in normal lactating mouse skin, demonstrating that the transcription of milk protein genes in lactating mouse skin is a normal event, and is not peculiar to the transgene. This surprising finding highlights the developmental relationship of the mammary gland to other specialized structures of the skin, supports a role for epithelial-extracellular matrix interactions in the regulation of milk protein gene expression in vivo, and identifies the skin as a particularly accessible model system in which to study the regulation of milk protein gene expression. In addition, the guinea-pig α-lactalbumin gene will be a source of regulatory sequences with which to direct heterologous gene expression to the sebaceous glands of transgenic mice.

Original languageEnglish (US)
Pages (from-to)459-467
Number of pages9
JournalBiochemical Journal
Volume275
Issue number2
DOIs
StatePublished - 1991

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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