{"doi":"10.1111/cas.12006","title":"Development of an early induction model of medulloblastoma in Ptch1 heterozygous mice initiated with <i>N</i>‐ethyl‐<i>N</i>‐nitrosourea","abstract":"<jats:p>Mice heterozygous for the <jats:italic>ptch1</jats:italic> 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 <jats:italic><jats:styled-content style=\"fixed-case\">N</jats:styled-content></jats:italic>‐ethyl‐<jats:italic><jats:styled-content style=\"fixed-case\">N</jats:styled-content></jats:italic>‐nitrosourea (<jats:styled-content style=\"fixed-case\">ENU</jats:styled-content>). Ptch1 mice and their wild‐type littermates received a single intraperitoneal injection of <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> (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 (<jats:styled-content style=\"fixed-case\">EGL</jats:styled-content>), a possible origin of medulloblastoma, after injection of 100 mg <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">EGL</jats:styled-content> cells and misalignment of <jats:styled-content style=\"fixed-case\">P</jats:styled-content>urkinje cells were increased dose‐dependently. Although <jats:styled-content style=\"fixed-case\">EGL</jats:styled-content> was strikingly decreased after <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> injection, strong recovery was observed in mice of the d1‐treated group. In summary, neonatal treatment with <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> is available for the induction of medulloblastoma in ptch1 mice, and 10 mg of <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> administered on d1 appeared to be an appropriate dose to induce medulloblastoma.</jats:p>","journal":"Cancer Science","year":2012,"id":614502,"datarank":0.20794415416798362,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"self_citation_contribution":0.20794415416798362,"citation_network_contribution":0.0,"self_endowment_contribution":0.20794415416798362,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1583526,"name":"Saori Matsuo","orcid":null,"position":1,"is_corresponding":false},{"id":373871,"name":"Kaoru Inoue","orcid":"0000-0002-3615-6192","position":2,"is_corresponding":false},{"id":1583527,"name":"Kei Tamura","orcid":null,"position":3,"is_corresponding":false},{"id":1583528,"name":"Kaoru Irie","orcid":null,"position":4,"is_corresponding":false},{"id":1583530,"name":"Yukio Kodama","orcid":null,"position":5,"is_corresponding":false},{"id":1583532,"name":"Midori Yoshida","orcid":null,"position":6,"is_corresponding":false},{"id":1583525,"name":"Miwa Takahashi","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Development of an early induction model of medulloblastoma in Ptch1 heterozygous mice initiated with <i>N</i>‐ethyl‐<i>N</i>‐nitrosourea","abstract":"<jats:p>Mice heterozygous for the <jats:italic>ptch1</jats:italic> 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 <jats:italic><jats:styled-content style=\"fixed-case\">N</jats:styled-content></jats:italic>‐ethyl‐<jats:italic><jats:styled-content style=\"fixed-case\">N</jats:styled-content></jats:italic>‐nitrosourea (<jats:styled-content style=\"fixed-case\">ENU</jats:styled-content>). Ptch1 mice and their wild‐type littermates received a single intraperitoneal injection of <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> (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 (<jats:styled-content style=\"fixed-case\">EGL</jats:styled-content>), a possible origin of medulloblastoma, after injection of 100 mg <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> 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 <jats:styled-content style=\"fixed-case\">EGL</jats:styled-content> cells and misalignment of <jats:styled-content style=\"fixed-case\">P</jats:styled-content>urkinje cells were increased dose‐dependently. Although <jats:styled-content style=\"fixed-case\">EGL</jats:styled-content> was strikingly decreased after <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> injection, strong recovery was observed in mice of the d1‐treated group. In summary, neonatal treatment with <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> is available for the induction of medulloblastoma in ptch1 mice, and 10 mg of <jats:styled-content style=\"fixed-case\">ENU</jats:styled-content> administered on d1 appeared to be an appropriate dose to induce medulloblastoma.</jats:p>","is_dataset_classified":null,"base_score":1.3862943611198906,"endowment":1.3862943611198906,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"22937732","pmcid":"PMC7659221","openalex_id":"https://openalex.org/W1995837164","authors":[],"funders":[],"total_grants":0,"fwci":0.2455,"citation_percentile":0.53519812,"influential_citations":0,"citation_trend":[{"year":2013,"count":1},{"year":2014,"count":1},{"year":2025,"count":1}],"oa_status":"green","license":"http://onlinelibrary.wiley.com/termsAndConditions#vor","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7659221","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/7659221","host_type":"repository"},{"url":"https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1111%2Fcas.12006","host_type":"publisher"},{"url":"https://onlinelibrary.wiley.com/doi/pdf/10.1111/cas.12006","host_type":"publisher"},{"url":"https://doi.org/10.1111/cas.12006","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/22937732","host_type":"repository"}],"fields_of_study":["Hedgehog Signaling Pathway Studies","Glioma Diagnosis and Treatment","Developmental Biology and Gene Regulation"],"mesh_terms":["Patched Receptors","Patched-1 Receptor","Alkylating Agents","Animals","Brain Neoplasms","Ethylnitrosourea","Heterozygote","Medulloblastoma","Purkinje Cells","Receptors, Cell Surface","Mice, Knockout","Mice"],"keywords":["Medulloblastoma","PTCH1","Biology","Immunohistochemistry","Intraperitoneal injection","Internal medicine","Andrology","Medicine","Endocrinology","Pathology","Cancer research","Genetics","Sonic hedgehog"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-02T13:50:08.880221Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}