Cysteine to tyrosine substitution at position 282 (p.C282Y)
Figure 12.10 Schematic of HFE protein. Hypothetical model of HLA-H protein based on similarity to MHC class I proteins as proposed by Feder et al. with the positions of the mutations they identified shown. Redrawn and reprinted by permission from Macmillan Publishers Ltd: Nature Genetics (Feder et al. 1996), copyright 1996.
The HFE gene in mice is structurally identical to that in humans (Riegert et al. 1998). This has allowed both knock-out studies and analysis of the effects of specific mutations. HFE knock-out mice show impaired iron homeostasis with elevated transfer-rin saturations and hepatic iron loading (Zhou et al.
1998). Iron overloading mimicking human haemo-chromatosis was seen in knock-in mice homozygous for the C282Y mutation: the effects of the mutation were not, however, to produce a null allele (in other words to give no gene product or product activity) (Levy et al. 1999).
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