A mouse model of hereditary coproporphyria identified in an ENU mutagenesis screen

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dc.contributor.authorConway, A.J.
dc.contributor.authorBrown, F.C.
dc.contributor.authorFullinfaw, R.O.
dc.contributor.authorKile, B.T.
dc.contributor.authorJane, S.M.
dc.contributor.authorCurtis, D.J.
dc.date.issued2017
dc.description.abstractA genome-wide ethyl-N-nitrosourea (ENU) mutagenesis screen in mice was performed to identify novel regulators of erythropoiesis. Here, we describe a mouse line, RBC16, which harbours a dominantly inherited mutation in the Cpox gene, responsible for production of the haem biosynthesis enzyme, coproporphyrinogen III oxidase (CPOX). A premature stop codon in place of a tryptophan at amino acid 373 results in reduced mRNA expression and diminished protein levels, yielding a microcytic red blood cell phenotype in heterozygous mice. Urinary and faecal porphyrins in female RBC16 heterozygotes were significantly elevated compared with that of wild-type littermates, particularly coproporphyrinogen III, whereas males were biochemically normal. Attempts to induce acute porphyric crises were made using fasting and phenobarbital treatment on females. While fasting had no biochemical effect on RBC16 mice, phenobarbital caused significant elevation of faecal coproporphyrinogen III in heterozygous mice. This is the first known investigation of a mutagenesis mouse model with genetic and biochemical parallels to hereditary coproporphyria.
dc.description.statementofresponsibilityAshlee J. Conway, Fiona C. Brown, Robert O. Fullinfaw, Benjamin T. Kile, Stephen M. Jane and David J. Curtis
dc.identifier.citationDisease Models and Mechanisms, 2017; 10(8):1005-1013
dc.identifier.doi10.1242/dmm.029116
dc.identifier.issn1754-8403
dc.identifier.issn1754-8411
dc.identifier.orcidKile, B.T. [0000-0002-8836-8947]
dc.identifier.urihttp://hdl.handle.net/2440/126693
dc.language.isoen
dc.publisherCompany of Biologists
dc.rights© 2017. Published by The Company of Biologists Ltd.
dc.source.urihttps://doi.org/10.1242/dmm.029116
dc.subjectEthyl-N-nitrosourea; hereditary coproporphyria; CPOX; anaemia
dc.titleA mouse model of hereditary coproporphyria identified in an ENU mutagenesis screen
dc.typeJournal article
pubs.publication-statusPublished

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