Gene expression profiling of Hfe-/-liver and duodenum in mouse strains with differing susceptibilities to iron loading: identification of transcriptional regulatory targets of Hfe and potential hemochromatosis modifiers

Table 5 Changes in expression of genes involved in iron metabolism

Gene	Protein	Major biochemical activity	Role	Organ	S-score
					D2 KO versus D2 WT	B6 KO versus B6 WT	D2 WT versus B6 WT
Iron storage
Ftl1	Ferritin L chain	Fe mineralization	Cytosolic storage	Liver	+1.70	+2.24	NS
Iron transport
Slc40a1	Ferroportin	Membrane transporter	Cellular export	Liver	+3.18	+4.89	+3.94
Abcg2	Bcrp	Membrane transporter	Possible mitochondrial heme export	Liver	+2.97	NS	NS
Sfxn2	Sideroflexin2	Membrane transporter	Mitochondrial traffic	Liver	-2.38	-2.16	NS
Slc25a37	Mitoferrin	Membrane transporter	Mitochondrial traffic	Liver	NS	+2.28	NS
Lcn2	Lipocalin2	Siderophore iron binding	Traffic of siderophore-bound iron	Liver	-2.91	NS	NS
Receptors
Tfrc	Transferrin receptor1	Transferrin binding	Transferrin iron uptake	Duodenum	-2.07	NS	NS
Lrp1	LRP/CD91	Hemoplexin receptor	Hemoplexin uptake	Liver	NS	-2.03	NS
Regulators
Ireb2	IRP2	RNA binding	Control of cellular iron	Duodenum	+2.26	NS	-2.64
Hamp1	Hepcidin 1	Ferroportin binding	Control of systemic iron	Liver	-6.27	NS	-3.57
Hamp2	Hepcidin 2	?	?	Liver	-3.40	NS	+3.36
Hfe	HFE	TfR1 binding	?	Liver	-7.96	-8.96	-3.16
				Duodenum	-5.70	-7.32	NS
Hfe2	HJV	Neogenin binding	Control of hepcidin expression	Liver	NS	-2.01	NS
Fxn	Frataxin	Iron binding	Chaperon for Fe-S synthesis	Liver	NS	NS	-3.09
Smad4	Smad4	Transcription factor	Control of hepcidin expression	Liver	NS	NS	-3.59
				Duodenum	NS	NS	-5.05
Usf2	Usf2	Transcription factor	Control of hepcidin expression	Liver	NS	+2.08	NS
Oxidoreductases
Cybrd1	Dcytb	Fe(III) reduction	Facilitates duodenal transport by DMT1	Duodenum	+2.97	NS	NS

Iron metabolism genes are cited in this table where significant expression variations in Hfe^-/- mice (knockout [KO]) or expression differences between wild-type (WT) strains were detected. S-scores were obtained as described in Material and Methods and are proportional to fold changes. Positive S-scores indicate that the genes are more highly expressed in KO than in WT mice, or in WT D2 than in WT B6 mice. NS, not significant.

ISSN: 1474-760X