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dc.contributor.authorRogers, Michael S.
dc.contributor.authorBoyartchuk, Victor L.
dc.contributor.authorRohan, Richard M.
dc.contributor.authorBirsner, Amy E.
dc.contributor.authorDietrich, William F.
dc.contributor.authorD'Amato, Robert J.
dc.date2022-08-11T08:10:15.000
dc.date.accessioned2022-08-23T17:01:24Z
dc.date.available2022-08-23T17:01:24Z
dc.date.issued2012-05-15
dc.date.submitted2012-10-10
dc.identifier.citation<p>Rogers MS, Boyartchuk V, Rohan RM, Birsner AE, Dietrich WF, et al. (2012) The Classical Pink-Eyed Dilution Mutation Affects Angiogenic Responsiveness. PLoS ONE 7(5): e35237. doi:10.1371/journal.pone.0035237. <a href="http://dx.doi.org/10.1371/journal.pone.0035237" target="_blank">Link to article on publisher's website</a></p>
dc.identifier.issn1932-6203
dc.identifier.doi10.1371/journal.pone.0035237
dc.identifier.pmid22615734
dc.identifier.urihttp://hdl.handle.net/20.500.14038/44001
dc.description.abstractAngiogenesis is the process by which new blood vessels are formed from existing vessels. Mammalian populations, including humans and mice, harbor genetic variations that alter angiogenesis. Angiogenesis-regulating gene variants can result in increased susceptibility to multiple angiogenesis-dependent diseases in humans. Our efforts to dissect the complexity of the genetic diversity that regulates angiogenesis have used laboratory animals due to the availability of genome sequence for many species and the ability to perform high volume controlled breeding. Using the murine corneal micropocket assay, we have observed more than ten-fold difference in angiogenic responsiveness among various mouse strains. This degree of difference is observed with either bFGF or VEGF induced corneal neovascularization. Ongoing mapping studies have identified multiple loci that affect angiogenic responsiveness in several mouse models. In this study, we used F2 intercrosses between C57BL/6J and the 129 substrains 129P1/ReJ and 129P3/J, as well as the SJL/J strain, where we have identified new QTLs that affect angiogenic responsiveness. In the case of AngFq5, on chromosome 7, congenic animals were used to confirm the existence of this locus and subcongenic animals, combined with a haplotype-based mapping approach that identified the pink-eyed dilution mutation as a candidate polymorphism to explain AngFq5. The ability of mutations in the pink-eyed dilution gene to affect angiogenic response was demonstrated using the p-J allele at the same locus. Using this allele, we demonstrate that pink-eyed dilution mutations in Oca2 can affect both bFGF and VEGF-induced corneal angiogenesis.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=22615734&dopt=Abstract">Link to article in PubMed</a>
dc.rights<p>Copyright: © 2012 Rogers et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</p>
dc.subjectAnimals
dc.subjectEye Color
dc.subjectHaplotypes
dc.subjectMice
dc.subjectMice, Inbred C57BL
dc.subjectMutation
dc.subjectNeovascularization, Physiologic
dc.subjectPolymorphism, Genetic
dc.subjectGenetics and Genomics
dc.titleThe classical pink-eyed dilution mutation affects angiogenic responsiveness
dc.typeJournal Article
dc.source.journaltitlePLoS One
dc.source.volume7
dc.source.issue5
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1209&amp;context=pgfe_pp&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pgfe_pp/209
dc.identifier.contextkey3384670
refterms.dateFOA2022-08-23T17:01:24Z
html.description.abstract<p>Angiogenesis is the process by which new blood vessels are formed from existing vessels. Mammalian populations, including humans and mice, harbor genetic variations that alter angiogenesis. Angiogenesis-regulating gene variants can result in increased susceptibility to multiple angiogenesis-dependent diseases in humans. Our efforts to dissect the complexity of the genetic diversity that regulates angiogenesis have used laboratory animals due to the availability of genome sequence for many species and the ability to perform high volume controlled breeding. Using the murine corneal micropocket assay, we have observed more than ten-fold difference in angiogenic responsiveness among various mouse strains. This degree of difference is observed with either bFGF or VEGF induced corneal neovascularization. Ongoing mapping studies have identified multiple loci that affect angiogenic responsiveness in several mouse models. In this study, we used F2 intercrosses between C57BL/6J and the 129 substrains 129P1/ReJ and 129P3/J, as well as the SJL/J strain, where we have identified new QTLs that affect angiogenic responsiveness. In the case of AngFq5, on chromosome 7, congenic animals were used to confirm the existence of this locus and subcongenic animals, combined with a haplotype-based mapping approach that identified the pink-eyed dilution mutation as a candidate polymorphism to explain AngFq5. The ability of mutations in the pink-eyed dilution gene to affect angiogenic response was demonstrated using the p-J allele at the same locus. Using this allele, we demonstrate that pink-eyed dilution mutations in Oca2 can affect both bFGF and VEGF-induced corneal angiogenesis.</p>
dc.identifier.submissionpathpgfe_pp/209
dc.contributor.departmentProgram in Gene Function and Expression
dc.source.pagese35237


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