title: Elf5 is essential for early embryogenesis and mammary gland development during pregnancy and lactation.
abstract: 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.
authors.affiliation: Centre for Functional Genomics and Human Disease, Monash Institute of Reproduction and Development, Monash University, Melbourne, Victoria, Australia.
authors.forename: Jiong
authors.initials: J
authors.lastname: Zhou
authors.forename: Renee
authors.initials: R
authors.lastname: Chehab
authors.forename: Josephine
authors.initials: J
authors.lastname: Tkalcevic
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Naylor
authors.forename: Jessica
authors.initials: J
authors.lastname: Harris
authors.forename: Trevor J
authors.initials: TJ
authors.lastname: Wilson
authors.forename: Sue
authors.initials: S
authors.lastname: Tsao
authors.forename: Irene
authors.initials: I
authors.lastname: Tellis
authors.forename: Silva
authors.initials: S
authors.lastname: Zavarsek
authors.forename: Dakang
authors.initials: D
authors.lastname: Xu
authors.forename: Erika J
authors.initials: EJ
authors.lastname: Lapinskas
authors.forename: Jane
authors.initials: J
authors.lastname: Visvader
authors.forename: Geoffrey J
authors.initials: GJ
authors.lastname: Lindeman
authors.forename: Ross
authors.initials: R
authors.lastname: Thomas
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Ormandy
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Hertzog
authors.forename: Ismail
authors.initials: I
authors.lastname: Kola
authors.forename: Melanie A
authors.initials: MA
authors.lastname: Pritchard
mesh_terms: D000818:Animals; D001483:Base Sequence; D004247:DNA / Q000235:genetics; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D047109:Fetal Development / Q000235:genetics / Q000502:physiology*; D018507:Gene Expression Regulation, Developmental; D006579:Heterozygote; D007774:Lactation; D008321:Mammary Glands, Animal / Q000254:growth & development* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D011247:Pregnancy; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: D012333:RNA, Messenger; D011981:Receptors, Prolactin; D014157:Transcription Factors; D004247:DNA