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  • The EMBO Journal (2005) 24, 635 - 644
  • doi:10.1038/sj.emboj.7600538

Published online: 13 January 2005

Elf5 is essential for early embryogenesis and mammary gland development during pregnancy and lactation

Jiong Zhou1,a, Renee Chehab1, Josephine Tkalcevic1, Matthew J Naylor2, Jessica Harris2, Trevor J Wilson1, Sue Tsao1, Irene Tellis1, Silva Zavarsek1, Dakang Xu1, Erika J Lapinskas1, Jane Visvader3, Geoffrey J Lindeman3, Ross Thomas1, Christopher J Ormandy2, Paul J Hertzog1, Ismail Kola1,b and Melanie A Pritchard1

  1. Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia
  2. Garvan Institute of Medical Research, Darlinghurst, NSW, Australia
  3. The Walter and Eliza Hall Institute of Medical Research, Melbourne, Victoria, Australia

Correspondence to:

Melanie A Pritchard, Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia. Tel.: +61 3 9594 7208; Fax: +61 3 9594 7211; E-mail E-mail: melanie.pritchard@med.monash.edu.au

aPresent address: Prince Henry's Institute of Medical Research, Monash Medical Centre, Clayton, Australia

bPresent address: Merck Research Laboratories, Merck & Co., Inc., Rahway, NJ, USA

Received 10 August 2004; Accepted 8 December 2004

Elf5 is an epithelial-specific ETS factor. Embryos with a null mutation in the Elf5 gene died before embryonic day 7.5, indicating that Elf5 is essential during mouse embryogenesis. Elf5 is also required for proliferation and differentiation of mouse mammary alveolar epithelial cells during pregnancy and lactation. The loss of one functional allele led to complete developmental arrest of the mammary gland in pregnant Elf5 heterozygous mice. A quantitative mRNA expression study and Western blot analysis revealed that decreased expression of Elf5 correlated with the downregulation of milk proteins in Elf5+/- mammary glands. Mammary gland transplants into Rag-/- mice demonstrated that Elf5+/- mammary alveolar buds failed to develop in an Elf5+/+ mammary fat pad during pregnancy, demonstrating an epithelial cell autonomous defect. Elf5 expression was reduced in Prolactin receptor (Prlr) heterozygous mammary glands, which phenocopy Elf5+/- glands, suggesting that Elf5 and Prlr are in the same pathway. Our data demonstrate that Elf5 is essential for developmental processes in the embryo and in the mammary gland during pregnancy.

  • Keywords:

    • ETS,
    • mammary gland,
    • milk protein genes,
    • prolactin,
    • prolactin receptor