Reference SummaryReilly KM, Proc Natl Acad Sci U S A 2004 Aug 31;101(35):13008-13
Title |
Susceptibility to astrocytoma in mice mutant for Nf1 and Trp53 is linked to chromosome 11 and subject to epigenetic effects. | ||||
Authors |
Reilly KM; Tuskan RG; Christy E; Loisel DA; Ledger J; Bronson RT; Smith CD; Tsang S; Munroe DJ; Jacks T | ||||
Journal |
Proc Natl Acad Sci U S A | ||||
Volume |
101 | ||||
Issue |
35 | ||||
Year |
2004 | ||||
Pages |
13008-13 | ||||
Abstract |
Astrocytoma is the most common malignant brain tumor in humans. Loss of the p53 signaling pathway and up-regulation of the ras signaling pathway are common during tumor progression. We have shown previously that mice mutant for Trp53 and Nf1 develop astrocytoma, progressing to glioblastoma, on a C57BL/6J strain background. In contrast, here we present data that mice mutant for Trp53 and Nf1 on a 129S4/SvJae background are highly resistant to developing astrocytoma. Through analysis of F1 progeny, we demonstrate that susceptibility to astrocytoma is linked to chromosome 11, and that the modifier gene(s) responsible for differences in susceptibility is closely linked to Nf1 and Trp53. Furthermore, this modifier of astrocytoma susceptibility is itself epigenetically modified. These data demonstrate that epigenetic effects can have a strong effect on whether cancer develops in the context of mutant ras signaling and mutant p53, and that this mouse model of astrocytoma can be used to identify modifier phenotypes with complex inheritance patterns that would be unidentifiable in humans. Because analysis of gene function in the mouse is often performed on a mixed C57BL/6,129 strain background, these data also provide a powerful example of the potential of these strains to mask interesting gene functions. | ||||
Links |
J:92444 – MGI References 15319471 – National Library of Medicine/PubMed |
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Strain Notes
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| Strain | Model Name | Treatment Agent(s) | Organ Affected | Frequency | Model Details |
|---|---|---|---|---|---|
| B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Adrenal gland - Medulla pheochromocytoma | Adrenal gland - Medulla |
12 |
||
| 129S4.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Adrenal gland - Medulla pheochromocytoma | Adrenal gland - Medulla |
3.0 |
||
| (CBA/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | Adrenal gland - Medulla pheochromocytoma | Adrenal gland - Medulla |
12 |
||
| B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
71 |
||
| 129S4.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
21 |
||
| (129S4/SvJae x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
32 |
||
| (129S4.129S2 x C57BL/6J)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
73 |
||
| (C57BL/6J x 129S4.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
52 |
||
| (A/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
85 |
||
| (DBA/2J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
80 |
||
| (CBA/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | CNS - Brain - Astrocyte astrocytoma | CNS - Brain - Astrocyte |
31 |
||
| B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
29 |
||
| 129S4.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
21 |
||
| (CBA/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | Leukocyte - Monocyte - Macrophage - Histiocyte histiocytic sarcoma | Leukocyte - Monocyte - Macrophage - Histiocyte |
29 |
||
| B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Leukocyte lymphoma | Leukocyte |
16 |
||
| 129S4.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Leukocyte lymphoma | Leukocyte |
6.1 |
||
| (CBA/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | Leukocyte lymphoma | Leukocyte |
16 |
||
| B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
64 |
||
| 129S4.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
64 |
||
| (CBA/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + | Mesodermal cell/mesoblast sarcoma | Mesodermal cell/mesoblast |
64 |