LCN2-cTG mice Whole genome sequencing

Transgenic mice are a useful tool for exploring various aspects of gene function. A key element of this approach is the targeted overexpression of specific genes in cells or tissues. In this study, we report, for the first time, generation and characterization of lipocalin-2 (LCN2) conditional transgenic (cTg) mice. We generated the R26-LCN2 transgenic (LCN2-cTg) mice that carries a loxP-flanked STOP (neo) cassette followed by the Lcn2 gene and a GFP sequence. When bred to a Tg mouse expressing Cre recombinase under the control of various tissues or cell-specific promoters, Cre recombination deletes the STOP cassette and allows the expression of LCN2 and GFP. Here, we achieved the recombination of loxP-flanked LCN2-GFP in hippocampal astrocytes of the cTg mouse brain using a targeted delivery of adeno-associated virus (AAVs) bearing Cre recombinase under GFAP promoter (AAVs-GFAP-mCherry-Cre). These mice with localized LCN2 overexpression in astrocytes in the hippocampus developed neuroinflammation, with enhanced glial activation and increased mRNA and protein levels of pro-inflammatory cytokines, such as TNF-alpha and IL-1beta. Further, the mice showed an impairment of cognitive function as a typical symptom of hippocampal inflammation. Taken together, our study demonstrates the usefulness of LCN2-cTg mice to target specific cells in various organs for conditional LCN2 expression and for subsequent investigation of the functional role of cell type-specific LCN2 within these sites. Moreover, the LCN2-cTg mice with the targeted expression of LCN2 in hippocampal astrocytes are a new in vivo model of neuroinflammation.