Ferrochelatase Deficiency(Fech) Chr18

Ferrochelatase Deficiency (Fech), Chr. 18, 39.0 cM, Genome Coordinates: 6498828-65009641

The first allele for ferrochelatase deficiency was found in a mutagenesis experiment using ethylnitrosourea at the Institut Pasteur in 1998. A targeted mutation was subsequently created. Studies with the first allele revealed marked variability in the phenotype based on the genetic background. The mutated gene was mapped to Chromosome 18. On the BALB/cByJ background, jaundice can be seen as early as 2 weeks of age by the color of the serum and the yellow color of the unhaired and unpigmented ears. Photosensitivity may be a problem, particularly affecting the ears, under normal husbandry conditions, especially in cages close to the light source. Results vary based on the wavelength of the lamps used. In such cases ears become red and swollen. Tips of the pinna may undergo necrosis, ulceration, and autoamputation. Hepatomegaly and splenomegaly are progressive.

Livers accumulate proporphyrin IX as a brown crystalin material within canaliculi, interlobular biliary ducts, Kupffer cells, and the gall bladder. There is progressive portal and periportal fibrosis associated with increased pigment. Erythroid hyperplasia is a prominent feature in the spleen and bone marrow. Mice develop a normocytic anemia. Polychromasia, anisocytosis, target cells, and leptocytes can be found in blood smears.

This is a mouse model for human erythropoeitic protoporphyria (EPP) which is also associated with reduced activity of ferrochelatase.


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Shi Z; Ferreira GC, Probing the active site loop motif of murine ferrochelatase by random mutagenesis., J Biol Chem 2004 May 7;279(19):19977-86

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