Analysis of the mouse CSF-1 gene promoter in a transgenic mouse model

Sherry L. Abboud, Maria Bunegin, Nandini Ghosh-Choudhury, Kathleen Woodruff

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

CSF-1 stimulates monocyte and osteoclast populations. However, the molecular mechanisms involved in regulating CSF-1 gene expression are unclear. To identify regulatory regions that control normal CSF-1 gene expression, a - 774/+183-bp fragment of the murine CSF-1 promoter was analyzed in vitro and in vivo. Transcriptional activity was high in cultured osteoblasts that express CSF-1 mRNA compared to ARH-77 B cells that lack CSF-1 gene expression. Transient transfection of osteoblasts with promoter deletion constructs showed that the -774-bp fragment conferred the highest transcriptional activity and contained activator and repressor sequences. To assess the ability of the CSF-1 promoter to confer normal tissue expression of CSF-1, transgenic mice containing the -774/+183-bp region driving the E. coli β-galactosidase (lacZ) reporter gene were generated. β-Gal analysis of whole tissue extracts showed transgene expression in all tissues tested except liver and kidney. At the cellular level, the pattern of β-gal expression in the spleen, thymus, bone, lung, and testes of adult transgenic mice mimicked normal endogenous CSF-1 mRNA expression in non-transgenic littermates detected by in situ hybridization. This region also directed appropriate transgene expression to sites in other tissues known to synthesize CSF-1, with the exception of the liver and kidney. These findings indicate that the -774-bp fragment contains cis-acting elements sufficient to direct CSF-1 gene expression in many tissues. CSF-1 promoter/lacZ mice may be useful for studying the transcriptional mechanisms involved in regulating CSF-1 gene expression in tissues throughout development.

Original languageEnglish (US)
Pages (from-to)941-949
Number of pages9
JournalJournal of Histochemistry and Cytochemistry
Volume51
Issue number7
DOIs
StatePublished - Jul 1 2003

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Keywords

  • Gene expression
  • Macrophage colony-stimulating factor
  • Transgenic mice

ASJC Scopus subject areas

  • Anatomy
  • Histology

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