title: Development of an early induction model of medulloblastoma in Ptch1 heterozygous mice initiated with N-ethyl-N-nitrosourea.
abstract: Mice heterozygous for the ptch1 gene (ptch1 mice) are known as a valuable model of medulloblastoma, a common brain tumor in children. To increase the incidence and reduce the time required for tumor development, allowing for evaluation of modifier effects on medulloblastoma in a short time, we attempted to develop an early induction model of medulloblastoma in ptch1 mice initiated with N-ethyl-N-nitrosourea (ENU). Ptch1 mice and their wild-type littermates received a single intraperitoneal injection of ENU (10, 50 or 100 mg/kg) on postnatal day 1 (d1) or 4 (d4), and histopathological assessment of brains was conducted at 12 weeks of age. The width of the external granular layer (EGL), a possible origin of medulloblastoma, after injection of 100 mg ENU on d1 or d4 was measured in up to 21-day-old mice. Cerebellar size was apparently reduced at the 50 mg dose and higher regardless of genotype. Microscopically, early lesions of medulloblastomas occurred with a high incidence only in ptch1 mice receiving 10 mg on d1 or d4, but a significant increase was not observed in other groups. Persistent EGL cells and misalignment of Purkinje cells were increased dose-dependently. Although EGL was strikingly decreased after ENU injection, strong recovery was observed in mice of the d1-treated group. In summary, neonatal treatment with ENU is available for the induction of medulloblastoma in ptch1 mice, and 10 mg of ENU administered on d1 appeared to be an appropriate dose to induce medulloblastoma.
authors.affiliation: Division of Pathology, National Institute of Health Sciences, Setagaya-ku, Tokyo, Japan. mtakahashi@nihs.go.jp
authors.forename: Miwa
authors.initials: M
authors.lastname: Takahashi
authors.forename: Saori
authors.initials: S
authors.lastname: Matsuo
authors.forename: Kaoru
authors.initials: K
authors.lastname: Inoue
authors.forename: Kei
authors.initials: K
authors.lastname: Tamura
authors.forename: Kaoru
authors.initials: K
authors.lastname: Irie
authors.forename: Yukio
authors.initials: Y
authors.lastname: Kodama
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshida
mesh_terms: D000477:Alkylating Agents / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000139:chemically induced* / Q000473:pathology; D005038:Ethylnitrosourea; D006579:Heterozygote; D008527:Medulloblastoma / Q000139:chemically induced* / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D011689:Purkinje Cells / Q000473:pathology; D011956:Receptors, Cell Surface / Q000235:genetics*
chemical_list: D000477:Alkylating Agents; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D005038:Ethylnitrosourea