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

Aparna Kaul, Yi Hsien Chen, Ryan J. Emnett, Scott M. Gianino, David H. Gutmann

Research output: Contribution to journalLetter

10 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)708-716
Number of pages9
JournalGenesis
Volume51
Issue number10
DOIs
StatePublished - Oct 1 2013

Keywords

  • Astrocyte
  • Brain tumor
  • Genetically-engineered mice
  • Glioma
  • Neural stem cell
  • Pilocytic astrocytoma

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