Erythropoietic protoporphyria in the house mouse. A recessive inherited ferrochelatase deficiency with anemia, photosensitivity, and liver disease.

Abstract

A viable autosomal recessive mutation (named fch, or ferrochelatase deficiency) causing jaundice and anemia in mice arose in a mutagenesis experiment using ethylnitrosourea. Homozygotes (fch/fch) display a hemolytic anemia, photosensitivity, cholestasis, and severe hepatic dysfunction. Protoporphyrin is found at high concentration in erythrocytes, serum, and liver. Ferrochelatase activity in various tissues is 2.7-6.3% of normal. Heterozygotes (+/fch) are not anemic and have normal liver function; they are not sensitive to light exposure; ferrochelatase activity is 45-65% of normal. Southern blot analysis using a ferrochelatase cDNA probe reveals no gross deletion of the ferrochelatase gene. This is the first spontaneous form of erythropoietic protoporphyria in the house mouse. Despite the presence in the mouse of clinical and biochemical features unfrequent in the human, this mutation may represent a model for the human disease, especially in its severe form. (J. Clin.

Reversion of hepatobiliary alterations by bone marrow transplantation in a murine model of erythropoietic protoporphyria

“…38 In the murine EPP model, the Fech m1Pas /Fech m1Pas mutant mouse (BALB/cJ), homozygous deficient animals exhibit hemolytic anemia and increased protoporphyrin levels inducing photosensitivity, cholestasis, and severe hepatic dysfunc- tion. 18 Hepatic defects represent a major and constant feature: onset of hepatomegaly is very early. Both cutaneous photosensitivity and liver impairment are the result of the accumulation of mostly erythrocyte-derived porphyrins.…”

Neurite Degeneration Induced by Heme Deficiency Mediated via Inhibition of NMDA Receptor-Dependent Extracellular Signal-Regulated Kinase 1/2 Activation

“…The BALB/c Fech m1Pas mouse strain was obtained from the The Jackson Laboratory (Bar Harbor, ME). The Fech m1Pas mutant contains a point mutation in the ferrochelatase gene (Tutois et al, 1991;Davies et al, 2005). Mice were bred by homozygous mating and maintained in a negative pressure isolator at 21°C under reduced light to prevent skin lesions.…”

Molecular and Genetic Characterization of Ferrochelatase.

“…Biochemical studies demonstrate that the mutant shows 10 to 15% ferrochelatase activity of control level, although immunochemical experiments revealed that a normal size of ferrochelatase (-40 kDa) is present in normal levels (Bloomer et al 1987). Very recently, a viable autosomal recessive mutation causing jaundice and anemia in mice arose by a mutagenesis experiment using ethylnitrosourea (Tutois et al 1991). The mutant mice exhibits ferrochelatase activity at 2.7, 6.3 and 3.3% of normal levels in kidney, liver and spleen, respectively.…”