Table 1.
Transgenic and genetically engineered mouse models for glioblastoma multiforme
| Mouse Model | Significant Findings | References |
|---|---|---|
| RCAS-EGFR; tva-INK4a-ARF−/−
RCAS-EGFR; tva-INK4a-ARF+/− |
EGFR mutation alone is insufficient to induce glioma unless the loss of INK4a-ARF occurs concomitantly | Holland, 2000 |
| GFAP-V12Ha-ras; GFAP-EGFRVIII | Aberrant EGFR level is involved in glioma progression rather than initiation and it can give rise to both astrocytoma & oligodendrocytoma | Wei, 2006 |
| S100β-V-erb(EGFR); S100β-INK4a- ARF−/− S100β-V-erb(EGFR); S100β-INK4a- ARF+/− |
Rapid tumor development from low-grade to high-grade with shorter latency and increased penetration | Weiss, 2003 |
| CAGGS-Cre; EGFRVIII; INK4a−/−; PTEN−/− | EGFRVIII alone is insufficient to induce cell transformation and only when concomitant loss of tumor suppresser gene INK4a along with PTEN can promote a fully-penetrant, rapid onset malignant glioma that resembles to human GBM | Zhu, 2009 |
| TgG(ΔZ)T121; PTEN−/− (pRB inactivated through T21 expression) | PTEN inactivation in pRB-inactivated model gives rise to focal hypercellularity, enhancing astrocytoma invasiveness as well as promoting angiogenesis | Xiao, 2005 |
| RCAS-KRas; PTEN−/− | The mice display similar histopathological characteristics such as increased cell density, pseudopalisading necrosis, microvascular proliferation | Hu, 2005 |
| p53−/−; Nf1−/−; PTEN+/− | Heterozygosities of PTEN, Nf1 and p53 cause accelerated glioma formation similar to primary “de novo” GBM | Kwon, 2008 |
| Ntva-INK4a-ARF+/−; RCAS-KRas; RCAS-AKT | The deletion of INK4a-ARF locus in addition to the activation of KRas and AKT permits GBM formation from differentiated astrocytes as well as enhances gliomageneis from neural progenitors. | Uhrbom, 2002 |
| Nf1+/−; p53+/− | The mouse model displays different stages of glioma including GBM. | Reilly, 2000 |
| P53 −/−; Nf1−/−; GFAP-Cre P53+/−; Nf1−/−; GFAP-Cre P53+/−; Nf1+/−; GFAP-Cre |
TP53 loss prior to or concomitant to Nf1 loss is required for malignant astrocytoma formation when early loss of Nf1 fails to induce gliomagenesis | Zhu, 2011 |