{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T22:51:52Z","timestamp":1791240712276,"version":"4.1.0"},"reference-count":36,"publisher":"Radiation Research Society","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Radiation Research"],"published-print":{"date-parts":[[2025,10,10]]},"abstract":"<jats:p>Susceptibility to radiation-induced lung disease differs among people and among inbred strains of mice; C3H\/HeJ mice develop early onset distress from pneumonitis and C57BL\/6J mice present later onset pneumonitis with fibrosis. Previous studies revealed C3H\/HeJ alleles at a 28 Mb locus on chromosome 2 to be linked to early onset distress and at an 18 Mb locus on chromosome 17 (called Radpf1 for radiation-induced pulmonary fibrosis-1) to decrease fibrosis in whole-thorax irradiated mice. To potentially reduce these genomic intervals, parental chr17-subcongenic mice with 0.71 Mb of C3H\/HeJ alleles, and chr 2-congenic mice with region-spanning C3H\/HeJ alleles from 95 to 123 Mb, and four lines of subcongenic mice received 16 Gy whole thorax irradiation and were assessed for onset of respiratory distress and histological lung disease at distress. One hundred percent of irradiated C3H\/HeJ and C57BL\/6J mice exhibited respiratory distress from pneumonitis and pneumonitis with fibrosis (6.8% of lung), respectively, while 18\/19 chr17-subcongenic mice survived to 25 weeks post-treatment without symptoms of distress and with significantly decreased radiation-induced pulmonary fibrosis (0.3% of lung, P = 0.002). Of the chr2-subcongenics, mice of one line, which we refer to as Pneum1 (pneumonitis one), succumbed at an average of 20.2 6 1.1 weeks postirradiation in females and 26.3 6 1.2 weeks in males (P &gt; 0.22 vs. congenic mice), reducing this locus to 5.6 Mb. Bioinformatic analyses revealed 114 candidate genes within these reduced intervals, with effects on pathways including on immune pathways. Mapping refined genetic susceptibility to radiation-induced lung disease in mice.<\/jats:p>","DOI":"10.1667\/rade-25-00064.1","type":"journal-article","created":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T00:01:37Z","timestamp":1760054497000},"page":"595-603","source":"Crossref","is-referenced-by-count":0,"title":["Genomic Loci of Radiation-induced Lung Disease in a Mouse Model: Refinement and Candidate Gene Analysis"],"prefix":"10.1667","volume":"204","author":[{"given":"Ian","family":"Johnson","sequence":"first","affiliation":[{"name":"Physics Department, I.K. Barber Faculty of Science, The University of British Columbia Okanagan, Kelowna, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicole","family":"Ferreira","sequence":"additional","affiliation":[{"name":"Physics Department, I.K. Barber Faculty of Science, The University of British Columbia Okanagan, Kelowna, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vassilena","family":"Sharlandjieva","sequence":"additional","affiliation":[{"name":"Physics Department, I.K. Barber Faculty of Science, The University of British Columbia Okanagan, Kelowna, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Sabatier","sequence":"additional","affiliation":[{"name":"Meakins-Christie Laboratories, McGill University, Montreal, PQ, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Hyde","sequence":"additional","affiliation":[{"name":"Physics Department, I.K. Barber Faculty of Science, The University of British Columbia Okanagan, Kelowna, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erin E.","family":"McCurry","sequence":"additional","affiliation":[{"name":"Physics Department, I.K. Barber Faculty of Science, The University of British Columbia Okanagan, Kelowna, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirsty","family":"Milligan","sequence":"additional","affiliation":[{"name":"Physics Department, I.K. Barber Faculty of Science, The University of British Columbia Okanagan, Kelowna, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina K.","family":"Haston","sequence":"additional","affiliation":[{"name":"Physics Department, I.K. Barber Faculty of Science, The University of British Columbia Okanagan, Kelowna, BC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1243","reference":[{"key":"2","doi-asserted-by":"crossref","unstructured":"MR McFarlane, KA Hochstedler, AM Laucis, et al.  \"Int J Radiation Oncol Biol Phys.\"  111, \"Predictors of pneumonitis after conventionally fractionated radiotherapy for locally advanced lung cancer.\" 1176 (2021)","DOI":"10.1016\/j.ijrobp.2021.07.1691"},{"key":"3","doi-asserted-by":"crossref","unstructured":"A Saha, M Beasley, N Hatton, et al.  \"Radiother Oncol.\"  156, \"Clinical and dosimetric predictors of radiation pneumonitis in early-stage lung cancer treated with stereotactic ablative Radiotherapy (SABR) \u2013 An analysis of UK's largest cohort of lung SABR patients.\" 153 (2020)","DOI":"10.1016\/j.radonc.2020.12.015"},{"key":"4","doi-asserted-by":"crossref","unstructured":"ME Aguado-Barrera, P Sosa-Fajardo, A G\u00f3mez-Caama\u00f1o, et al.  \"Lung Cancer.\"  176, \"Radiogenomics in lung cancer: Where are we?\" 56 (2023)","DOI":"10.1016\/j.lungcan.2023.01.001"},{"key":"5","unstructured":"E Naderi, ME Aguado-Barrera, LMH Schack, et al.  \"JNCI Cancer Spectr.\"  7, \"Large-scale meta-genome-wide association study reveals common genetic factors linked to radiation-induced acute toxicities across cancer types.\" pkad088 (2023)"},{"key":"6","doi-asserted-by":"crossref","unstructured":"R Thomas, YH Chen, H Hatabu, et al.  \"Lung Cancer.\"  145, \"Radio-graphic patterns of symptomatic radiation pneumonitis in lung cancer patients: Imaging predictors for clinical severity and outcome.\" 132 (2020)","DOI":"10.1016\/j.lungcan.2020.03.023"},{"key":"8","doi-asserted-by":"crossref","unstructured":"S Curras-Alonso, J Soulier, T Defard, et al.  \"Nat Commun.\"  14, \"An interactive murine single-cell atlas of the lung responses to radiation injury.\" 2445 (2023)","DOI":"10.1038\/s41467-023-38134-z"},{"key":"9","doi-asserted-by":"crossref","unstructured":"A Paun, AM Lemay, CK Haston,  \"Radiat Res.\"  173, \"Gene expression profiling distinguishes radiation-induced fibrosing alveolitis from alveolitis in mice.\" 512 (2010)","DOI":"10.1667\/RR1798.1"},{"key":"11","doi-asserted-by":"crossref","unstructured":"A Paun, ME Bergeron, CK Haston,  \"Sci Rep.\"  7, \"The Th1\/Th17 balance dictates the fibrosis response in murine radiation-induced lung disease.\" 11586 (2017)","DOI":"10.1038\/s41598-017-11656-5"},{"key":"12","doi-asserted-by":"crossref","unstructured":"A Paun, J Fox, V Balloy, et al.  \"Int J Radiat Oncol Biol Phys.\"  77, \"Combined Tlr2 and Tlr4 deficiency increases radiation-induced pulmonary fibrosis in mice.\" 1198 (2010)","DOI":"10.1016\/j.ijrobp.2009.12.065"},{"key":"13","doi-asserted-by":"crossref","unstructured":"AM Lemay  and CK Haston  \"Radiat Res.\"  170, \"Radiation-induced lung response of AcB\/BcA recombinant congenic mice.\" 299 (2008)","DOI":"10.1667\/RR1319.1"},{"key":"14","doi-asserted-by":"crossref","unstructured":"CK Haston, M Begin, G Dorion, et al.  \"Cancer Res.\"  67, \"Distinct loci influence radiation-induced alveolitis, from fibrosing alveolitis, in the mouse.\" 10796 (2007)","DOI":"10.1158\/0008-5472.CAN-07-2733"},{"key":"15","unstructured":"CK Haston, X Zhou, L Gumbiner-Russo, et al.  \"Cancer Res.\"  62, \"Universal and radiation-specific loci influence murine susceptibility to radiation-induced pulmonary fibrosis.\" 3782 (2002)"},{"key":"16","doi-asserted-by":"crossref","unstructured":"L Honeyman, M-E Bergeron, C Thang, et al.  \"Int J Radiat Biol.\"  101, \"A Chromosome 2 locus influences the onset of radiation-induced lung disease in mice.\" 581 (2025)","DOI":"10.1080\/09553002.2025.2473977"},{"key":"17","doi-asserted-by":"crossref","unstructured":"ME Bergeron, A Stefanov, CK Haston,  \"Mamm Genome.\"  29, \"Fine mapping of the major bleomycin-induced pulmonary fibrosis susceptibility locus in mice.\" 670 (2018)","DOI":"10.1007\/s00335-018-9774-3"},{"key":"18","doi-asserted-by":"crossref","unstructured":"AP Morgan, CP Fu, CY Kao, et al.  \"G3.\"  6, \"The Mouse Universal Genotyping Array: From substrains to subspecies.\" 263 (2016)","DOI":"10.1534\/g3.115.022087"},{"key":"20","unstructured":"CK Haston, CI Amos, TM King, et al.  \"Cancer Res.\"  56, \"Inheritance of susceptibility to bleomycin-induced pulmonary fibrosis in the mouse.\" 2596 (1996)"},{"key":"21","doi-asserted-by":"crossref","unstructured":"K Puthawala, N Hadjiangelis, SC Jacoby, et al.  \"Am J Respir Crit Care Med.\"  177, \"Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis.\" 82 (2008)","DOI":"10.1164\/rccm.200706-806OC"},{"key":"23","unstructured":"\"Genetics.\"  224, \"The Gene Ontology knowledge-base in 2023.\" kad088 (2023)"},{"key":"24","doi-asserted-by":"crossref","unstructured":"L Kolberg, U Raudvere, I Kuzmin, et al.  \"Nucleic Acids Res.\"  51, \"g: Profiler-interoperable web service for functional enrichment analysis and gene identifier mapping (2023 update).\" W130 (2023)","DOI":"10.1093\/nar\/gkad347"},{"key":"25","doi-asserted-by":"crossref","unstructured":"HW Tsao, S Anderson, KJ Finn, et al.  \"Immunity.\"  57, \"Targeting the aminopeptidase ERAP enhances antitumor immunity by disrupting the NKG2A-HLA-E inhibitory checkpoint.\" 2863 (2024)","DOI":"10.1016\/j.immuni.2024.10.013"},{"key":"26","doi-asserted-by":"crossref","unstructured":"A Jandke, D Melandri, L Monin, et al.  \"Nat Commun.\"  11, \"Butyrophilin-like proteins display combinatorial diversity in selecting and maintaining signature intraepithelial \u03b3\u03b4 T cell compartments.\" 3769 (2020)","DOI":"10.1038\/s41467-020-17557-y"},{"key":"27","doi-asserted-by":"crossref","unstructured":"H Harb, M Benamar, PS Lai, et al.  \"Immunity.\"  54, \"Notch4 signaling limits regulatory T-cell-mediated tissue repair and promotes severe lung inflammation in viral infections.\" 1186 (2021)","DOI":"10.1016\/j.immuni.2021.04.002"},{"key":"28","doi-asserted-by":"crossref","unstructured":"M Benamar, PS Lai, C-Y Huang, et al.  \"Allergy.\"  80, \"Notch4 regulatory T cells and SARS-CoV-2 viremia shape COVID19 survival outcome.\" 557 (2025)","DOI":"10.1111\/all.16333"},{"key":"29","doi-asserted-by":"crossref","unstructured":"S Braga-Cohen, J Lavigne, M Dos Santos, et al.  \"Int J Radiat Oncol Biol Phys.\"  121, \"Evidence of Alveolar macrophage metabolic shift following stereotactic body radiation therapy-induced lung fibrosis in mice.\" 506 (2025)","DOI":"10.1016\/j.ijrobp.2024.09.018"},{"key":"30","doi-asserted-by":"crossref","unstructured":"L Meziani, M Mondini, B Petit, et al.  \"Eur Respir J.\"  51, \"CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages.\" 1702120 (2018)","DOI":"10.1183\/13993003.02120-2017"},{"key":"32","doi-asserted-by":"crossref","unstructured":"E Monz\u00f3n-Casanova, R Rudolf, L Starick, et al.  \"J Immunol.\"  196, \"The forgotten: Identification and functional characterization of MHC class II molecules H2-Eb2 and RT1-Db2.\" 988 (2016)","DOI":"10.4049\/jimmunol.1403070"},{"key":"33","doi-asserted-by":"crossref","unstructured":"Z Tang, Y Wang, L Lv, et al.  \"PLoS One.\"  13, \"Mice with double knockout of H2-Eb1 and H2-Ab1 exhibit reduced susceptibility to allergic rhinitis.\" e0206122 (2018)","DOI":"10.1371\/journal.pone.0206122"},{"key":"34","doi-asserted-by":"crossref","unstructured":"CL Guh, KH Lei, YA Chen, et al.  \"Nucleic Acids Res.\"  51, \"RAD51 paralogs synergize with RAD51 to protect reversed forks from cellular nucleases.\" 11717 (2023)","DOI":"10.1093\/nar\/gkad856"},{"key":"35","doi-asserted-by":"crossref","unstructured":"M Yin, Z Liao, YJ Huang, et al.  \"PLoS One.\"  6, \"Polymorphisms of homologous recombination genes and clinical outcomes of non-small cell lung cancer patients treated with definitive radiotherapy.\" e20055 (2011)","DOI":"10.1371\/journal.pone.0020055"},{"key":"36","doi-asserted-by":"crossref","unstructured":"A Rashid, C Zeng, G Motta-Ribeiro, et al.  \"Sci Rep.\"  12, \"Proteomics of lung tissue reveals differences in inflammation and alveolar-capillary barrier response between atelectasis and aerated regions.\" 7065 (2022)","DOI":"10.1038\/s41598-022-11045-7"},{"key":"31","doi-asserted-by":"crossref","unstructured":"AM Groves, CJ Johnston, RS Misra, et al.  \"Radiat Res.\"  184, \"Whole-lung irradiation results in pulmonary macrophage alterations that are subpopulation and strain specific.\" 639 (2015)","DOI":"10.1667\/RR14178.1"},{"key":"22","doi-asserted-by":"crossref","unstructured":"M Ashburner, CA Ball, JA Blake, et al.  \"Nat Genet.\"  25, \"Gene ontology: tool for the unification of biology.\" 25 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