A dual reporter gene transgenic mouse demonstrates heterogeneity in hepatic fibrogenic cell populations

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Scott T MagnessDavid A Brenner

Abstract

Activation of hepatic stellate cells (HSCs) and other resident mesenchymal cells into myofibroblasts expressing alpha smooth muscle actin (alphaSMA) and collagen I is a key event in liver fibrogenesis. However, the temporal expression profiles of alphaSMA and collagen I genes in these cells is unknown. To address this question, we studied alphaSMA and collagen alpha1(I) transcriptional patterns in primary cultures of HSCs, and additionally, in an in vivo model of secondary biliary fibrosis using transgenic mice that express the Discomsoma sp. red fluorescent protein (RFP) and the enhanced green fluorescent protein (EGFP) reporter genes under direction of the mouse alphaSMA and collagen alpha1(I) promoter/enhancers, respectively. The alphaSMA-RFP mice were crossed with collagen-EGFP mice to generate double transgenic mice. Reporter gene expression in cultured HSCs demonstrated that both transgenes were induced at day 3 with continued expression through day 14. Interestingly, alphaSMA and collagen alpha1(I) transgenes were not coexpressed in all cells. Flow cytometry analysis showed three different patterns of gene expression: alphaSMA-RFP positive cells, collagen-EGFP positive cells, and cells expressing both transgenes. AlphaSM...Continue Reading

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Citations

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Jun 20, 2007·Pharmaceutical Research·Yuji Iimuro, David A Brenner
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