Reference SummaryReilly KM, Nat Genet 2000 Sep;26(1):109-13

Title

 Nf1;Trp53 mutant mice develop glioblastoma with evidence of strain-specific effects

Authors

 Reilly KM; Loisel DA; Bronson RT; McLaughlin ME; Jacks T

Journal

 Nat Genet

Volume

 26

Issue

 1

Year

 2000

Pages

 109-13

Abstract

 Astrocytomas are the leading cause of brain cancer in humans. Because these tumours are highly infiltrative, current treatments that rely on targeting the tumour mass are often ineffective. A mouse model for astrocytoma would be a powerful tool for dissecting tumour progression and testing therapeutics. Mouse models of astrocytoma have been designed to express oncogenic proteins in astrocytes, but have had limited success due to low tumour penetrance or limited tumour progression (1-3). We present here a mouse model of astrocytomas involving mutation of two tumour-suppressor genes, Nf1 and Trp53. Humans with mutations in NF1 develop neurofibromatosis type I (NF1) and have increased risk of optic gliomas, astrocytomas and glioblastomas (4,5). The TP53 tumour suppressor is often mutated in a subset of astrocytomas that develop at a young age and progress slowly to glioblastoma (termed secondary glioblastomas, in contrast to primary glioblastomas that develop rapidly de novo (6-10). This mouse model shows a range of astrocytoma stages, from low-grade astrocytoma to glioblastoma multiforme, and may accurately model human secondary glioblastoma involving TP53 loss. This is the first reported mouse model of astrocytoma initiated by loss of tumour suppressors, rather than overexpression of transgenic oncogenes.

Links

 J:64364 – MGI References
10973261 – National Library of Medicine/PubMed

Strain Notes

Strain Note
B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + Mice carrying both mutations on the same copy of chromosome 11 ("NPcis") were backcrossed to C57BL/6J for >8 generations.
Visual Summary Grid

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C57BL/6 CNS - Brain - Astrocyte astrocytoma CNS - Brain - Astrocyte

0
B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain - Astrocyte astrocytoma CNS - Brain - Astrocyte

73 - 92
(C3H/HeJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain - Astrocyte astrocytoma CNS - Brain - Astrocyte

75 - 100
(SJL/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain - Astrocyte astrocytoma CNS - Brain - Astrocyte

36 - 85
(CAST/EiJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain - Astrocyte astrocytoma CNS - Brain - Astrocyte

48 - 64
(C3H/HeJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain glioblastoma CNS - Brain

4.2
B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain glioblastoma CNS - Brain

0
(CAST/EiJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain glioblastoma CNS - Brain

14
(SJL/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + CNS - Brain glioblastoma CNS - Brain

9.1
B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

45
(C3H/HeJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

50
(SJL/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

73
(CAST/EiJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + Mesodermal cell/mesoblast sarcoma Mesodermal cell/mesoblast

43
B6.129S2-Nf1tm1Tyj Trp53tm1Tyj/+ + (Unspecified organ) tumor (Unspecified organ)

100
(C3H/HeJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + (Unspecified organ) tumor (Unspecified organ)

100
(SJL/J x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + (Unspecified organ) tumor (Unspecified organ)

100
(CAST/EiJ x B6.129S2)F1-Nf1tm1Tyj Trp53tm1Tyj/+ + (Unspecified organ) tumor (Unspecified organ)

100