This semi-dominant R59W point mutation provides a model for South African variegate porphyria. Heterozygotes have hepatic protoporphyrinogen oxidase activity that is 50% lower than wild-type and elevated concentrations of porphyrins and porphyrin precursors in the urine and feces. When fed 5-aminolevulinic acid the levels of phorphyrins excreted in the stool increases in a manner characteristic of acute variegate porphyria and these levels decrease subsequent to the removal of the 5-aminolevulinic acid from the diet. When bred to wild-type mates, heterozygotes produce approximately 50% heterozygous offspring, but heterozygous intercrosses do not produce homozygous pups, but do produce a percentage of heterozygous pups consistent with full penetrance and embryonic lethality of homozygotes.
The Ppoxtm1Had allele was generated in R1 ES Cells and subsequently backcrossed to C57BL/6J reaching N8 in 2004. In 2015 heterozygotes were shipped from Dr. Peter Meissner at University of Cape Town, South Africa, to Dr. Luanne Peters at The Jackson Laboratory. Sperm was cryopreserved from heterozygous males.
|Allele Name||targeted mutation 1, Harry A Dailey|
|Allele Type||Targeted (Hypomorph, Humanized sequence)|
|Gene Symbol and Name||Ppox, protoporphyrinogen oxidase|
|Strain of Origin||(129X1/SvJ x 129S1/Sv)F1-Kitl+|
|Molecular Note||A single codon was mutagenized to replace the arginine at amino acid 59 with tryptophan, mimicking the predominant variegate porphyria mutation in the South African human population, and a loxP flanked neomycin selection cassette was inserted into intron 2.|
When using the B6.129-Ppoxtm1Had/HadLlp mouse strain in a publication, please cite the originating article(s) and include JAX stock #028486 in your Materials and Methods section.