Reference SummaryPazzaglia S, Oncogene 2002 Oct 24;21(49):7580-4

Title

High incidence of medulloblastoma following X-ray-irradiation of newborn Ptc1 heterozygous mice.

Authors

Pazzaglia S; Mancuso M; Atkinson MJ; Tanori M; Rebessi S; Majo VD; Covelli V; Hahn H; Saran A

Journal

Oncogene

Volume

Issue

Year

2002

Pages

7580-4

Abstract

Individuals affected with the Gorlin syndrome inherit a germ-line mutation of the patched (Ptc1) developmental gene and, analogously to Ptc1 heterozygous mice, show an increased susceptibility to spontaneous tumor development. Human and mouse Ptc1 heterozygotes (Ptc1(+/-)) are also hypersensitive to ionizing radiation (IR)-induced tumorigenesis in terms of basal cell carcinoma (BCC) induction. We have analysed the involvement of Ptc1 in the tumorigenic response to a single dose of 3 Gy X-rays in neonatal and adult Ptc1 heterozygous and wild type mice. We report that irradiation dramatically increased the incidence of medulloblastoma development (51%) over the spontaneous rate (7%) in neonatal but not adult Ptc1 heterozygotes, indicating that medulloblastoma induction by IR is subjected to temporal restriction. Analysis of Ptc1 allele status in the tumors revealed loss of the wild type allele in 17 of 18 medulloblastomas from irradiated mice and in two of three spontaneous medulloblastomas. To our knowledge, irradiated newborn Ptc1(+/-) heterozygous mice constitute the first mouse model of IR-induced medulloblastoma tumorigenesis, providing a useful tool to elucidate the molecular basis of medulloblastoma development. doi:10.1038/sj.onc.1205973

Links

J:79666 – MGI References
12386820 – National Library of Medicine/PubMed

Strain Notes

Strain	Note
CD-1.129S2	Following an acute 3Gy whole body irradiation at 4 days, 33% of mice dead by 38 weeks. Only 10% of untreated mice were dead at the same age. Mice were maintained on CD-1 background, # of backcrossed unknown. Wild type littermates to targeted mutant mice.
CD-1.129S2-Ptch1^tm1Zim/+	90% of mice dead at 38 weeks following acute 3Gy dose x-irradiation given at 4 days old. Only 10% of untreated mice dead at the same age. Mice were maintained on CD-1 background.

Models
Strain	Model Name	Treatment Agent(s)	Organ Affected	Frequency
CD-1.129S2-Ptch1^tm1Zim/+	CNS - Brain - Undifferentiated cell medulloblastoma	X-radiation	CNS - Brain - Undifferentiated cell	0 - 51
CD-1.129S2-Ptch1^tm1Zim/+	CNS - Brain - Undifferentiated cell medulloblastoma		CNS - Brain - Undifferentiated cell	6.7 - 7.7
CD-1.129S2	CNS - Brain - Undifferentiated cell medulloblastoma	X-radiation	CNS - Brain - Undifferentiated cell	0
CD-1.129S2	CNS - Brain - Undifferentiated cell medulloblastoma		CNS - Brain - Undifferentiated cell	0
CD-1.129S2-Ptch1^tm1Zim/+	Leukocyte lymphoma	X-radiation	Thymus	2.4 - 25
CD-1.129S2-Ptch1^tm1Zim/+	Leukocyte lymphoma		Thymus	0 - 3.3
CD-1.129S2	Leukocyte lymphoma	X-radiation	Thymus	7 - 30
CD-1.129S2	Leukocyte lymphoma		Thymus	0 - 3.2
CD-1.129S2-Ptch1^tm1Zim/+	Mesodermal cell/mesoblast sarcoma	X-radiation	Mesodermal cell/mesoblast	7.8 - 37
CD-1.129S2-Ptch1^tm1Zim/+	Mesodermal cell/mesoblast sarcoma		Mesodermal cell/mesoblast	3.8 - 40
CD-1.129S2	Mesodermal cell/mesoblast sarcoma	X-radiation	Mesodermal cell/mesoblast	0
CD-1.129S2	Mesodermal cell/mesoblast sarcoma		Mesodermal cell/mesoblast	0
CD-1.129S2-Ptch1^tm1Zim/+	Skin - Epidermis - Basal cell carcinoma	X-radiation	Skin - Epidermis - Basal cell	0 - 15
CD-1.129S2-Ptch1^tm1Zim/+	(Unspecified organ) tumor		(Unspecified organ)	0 - 7.7
CD-1.129S2	(Unspecified organ) tumor	X-radiation	(Unspecified organ)	0 - 7
CD-1.129S2	(Unspecified organ) tumor		(Unspecified organ)	0