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Publication : Conditional KIAA1549:BRAF mice reveal brain region- and cell type-specific effects.

First Author  Kaul A Year  2013
Journal  Genesis Volume  51
Issue  10 Pages  708-16
PubMed ID  23893969 Mgi Jnum  J:204469
Mgi Id  MGI:5532621 Doi  10.1002/dvg.22415
Citation  Kaul A, et al. (2013) Conditional KIAA1549:BRAF mice reveal brain region- and cell type-specific effects. Genesis 51(10):708-16
abstractText  Low-grade brain tumors (pilocytic astrocytomas) that result from a genomic rearrangement in which the BRAF kinase domain is fused to the amino terminal of the KIAA1549 gene (KIAA1549:BRAF fusion; f-BRAF) commonly arise in the cerebellum of young children. To model this temporal and spatial specificity in mice, we generated conditional KIAA1549:BRAF strains that coexpresses green fluorescent protein (GFP). Although both primary astrocytes and neural stem cells (NSCs) from these mice express f-BRAF and GFP as well as exhibit increased MEK activity, only f-BRAF-expressing NSCs exhibit increased proliferation in vitro. Using Cre driver lines in which KIAA1549:BRAF expression was directed to NSCs (f-BRAF; BLBP-Cre mice), astrocytes (f-BRAF; GFAP-Cre mice), and NG2 progenitor cells (f-BRAF; NG2-Cre mice), increased glial cell numbers were observed only in the cerebellum of f-BRAF; BLBP-Cre mice in vivo. The availability of this unique KIAA1549:BRAF conditional transgenic mouse strain will enable future mechanistic studies aimed at defining the developmentally-regulated temporal and spatial determinants that underlie low-grade astrocytoma formation in children.
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