A Novel Mouse Model of Diffuse Intrinsic Pontine Glioma Initiated in Pax3-Expressing Cells

Neoplasia : an International Journal for Oncology Research
Katherine L MisuracaOren Becher

Abstract

Diffuse intrinsic pontine glioma (DIPG) is a rare and incurable brain tumor that arises predominately in children and involves the pons, a structure that along with the midbrain and medulla makes up the brainstem. We have previously developed genetically engineered mouse models of brainstem glioma using the RCAS/Tv-a system by targeting PDGF-B overexpression, p53 loss, and H3.3K27M mutation to Nestin-expressing brainstem progenitor cells of the neonatal mouse. Here we describe a novel mouse model targeting these same genetic alterations to Pax3-expressing cells, which in the neonatal mouse pons consist of a Pax3+/Nestin+/Sox2+ population lining the fourth ventricle and a Pax3+/NeuN+ parenchymal population. Injection of RCAS-PDGF-B into the brainstem of Pax3-Tv-a mice at postnatal day 3 results in 40% of mice developing asymptomatic low-grade glioma. A mixture of low- and high-grade glioma results from injection of Pax3-Tv-a;p53(fl/fl) mice with RCAS-PDGF-B and RCAS-Cre, with or without RCAS-H3.3K27M. These tumors are Ki67+, Nestin+, Olig2+, and largely GFAP- and can arise anywhere within the brainstem, including the classic DIPG location of the ventral pons. Expression of the H3.3K27M mutation reduces overall H3K27me3 as compar...Continue Reading

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Citations

Oct 21, 2017·Journal of Neuro-oncology·Masafumi MiyaiAkira Hara
Jan 21, 2018·Genes & Development·Faizaan Mohammad, Kristian Helin
Jan 30, 2019·Cancers·Fahim AhmadJayne M Stommel
Aug 30, 2019·Current Opinion in Oncology·Razina Aziz-Bose, Michelle Monje
May 28, 2020·Neuro-oncology·Phonphimon WongthidaRichard G Vile
Jun 16, 2018·Frontiers in Oncology·Christine HoemanOren J Becher
Oct 3, 2020·International Journal of Molecular Sciences·Maya S Graham, Ingo K Mellinghoff
Apr 5, 2017·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Tamara J Abou-AntounStephen M Dombrowski
Jul 9, 2020·Human Molecular Genetics·Anders M LindrothMassimo Squatrito
Jan 28, 2021·Immunity, Inflammation and Disease·Haitao LuoXingen Zhu
Jan 12, 2021·Chinese Neurosurgical Journal·Dilakshan SrikanthanJames T Rutka
Oct 22, 2020·Cell Reports·Ilango BalakrishnanSujatha Venkataraman
Jun 23, 2021·EBioMedicine·Gabrielle PriceConstantinos G Hadjipanayis

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Methods Mentioned

BETA
transgenic
genotyping
biopsy
xenograft

Software Mentioned

Region Statistics
GraphPad Prism
MetaMorph Premier
BrainSpan
Integrated Morphometry Analysis

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