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However, the effect of LMX1B mutations varies widely between individuals. To better understand the mechanisms underlying LMX1B-related phenotypes and individual differences, we backcrossed the Lmx1bV265D (also known as Lmx1bIcst) allele onto the C57BL\/6J (B6), 129\/Sj (129), C3A\/BLiA-Pde6b+\/J (C3H) and DBA\/2J-Gpnmb+ (D2-G) mouse strain backgrounds. Strain background had a significant effect on the onset and severity of ocular phenotypes in Lmx1bV265D\/+ mutant mice. Mice of the B6 background were the most susceptible to developing abnormal IOP distribution, severe anterior segment developmental anomalies (including malformed eccentric pupils, iridocorneal strands and corneal abnormalities) and glaucomatous nerve damage. By contrast, Lmx1bV265D mice of the 129 background were the most resistant to developing anterior segment abnormalities, had less severe IOP elevation than B6 mutants at young ages and showed no detectable nerve damage. To identify genetic modifiers of susceptibility to Lmx1bV265D-induced glaucoma-associated phenotypes, we performed a mapping cross between mice of the B6 (susceptible) and 129 (resistant) backgrounds. We identified a modifier locus on Chromosome 18, with the 129 allele(s) substantially lessening severity of ocular phenotypes, as confirmed by congenic analysis. By demonstrating a clear effect of genetic background in modulating Lmx1b-induced phenotypes, providing a panel of strains with different phenotypic severities and identifying a modifier locus, this study lays a foundation for better understanding the roles of LMX1B in glaucoma with the goal of developing new treatments.<\/jats:p>","DOI":"10.1242\/dmm.046953","type":"journal-article","created":{"date-parts":[[2021,1,18]],"date-time":"2021-01-18T10:45:21Z","timestamp":1610966721000},"source":"Crossref","is-referenced-by-count":37,"title":["Genetic background modifies vulnerability to glaucoma-related phenotypes in\n                    <i>Lmx1b<\/i>\n                    mutant mice"],"prefix":"10.1242","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3060-2999","authenticated-orcid":false,"given":"Nicholas G.","family":"Tolman","sequence":"first","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Ophthalmology, Columbia University Medical Center, and Zuckerman Mind Brain Behavior Institute, New York, NY 10027, USA"},{"name":"Graduate School of Biomedical Sciences, Tufts University School of Medicine, Boston, MA 02115, USA"},{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2209-0815","authenticated-orcid":false,"given":"Revathi","family":"Balasubramanian","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Ophthalmology, Columbia University Medical Center, and Zuckerman Mind Brain Behavior Institute, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3188-2611","authenticated-orcid":false,"given":"Danilo G.","family":"Macalinao","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3054-8769","authenticated-orcid":false,"given":"Alison L.","family":"Kearney","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2766-0976","authenticated-orcid":false,"given":"Katharine H.","family":"MacNicoll","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christa L.","family":"Montgomery","sequence":"additional","affiliation":[{"name":"Howard Hughes Medical Institute, Department of Ophthalmology, Columbia University Medical Center, and Zuckerman Mind Brain Behavior Institute, New York, NY 10027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8229-9357","authenticated-orcid":false,"given":"Wilhelmine N.","family":"de Vries","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6526-0688","authenticated-orcid":false,"given":"Ian J.","family":"Jackson","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6518-6449","authenticated-orcid":false,"given":"Sally H.","family":"Cross","sequence":"additional","affiliation":[{"name":"MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh EH4 2XU, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3755-6101","authenticated-orcid":false,"given":"Krishnakumar","family":"Kizhatil","sequence":"additional","affiliation":[{"name":"The Jackson Laboratory, Bar Harbor, ME 04609, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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