Targeted disruption of the hepatic transferrin receptor 2 gene in mice leads to iron overload

Wallace, Daniel F., Summerville, Lesa and Subramaniam, V. Nathan (2007) Targeted disruption of the hepatic transferrin receptor 2 gene in mice leads to iron overload. Gastroenterology, 132 1: 301-310. doi:10.1053/j.gastro.2006.11.028

Author Wallace, Daniel F.
Summerville, Lesa
Subramaniam, V. Nathan
Title Targeted disruption of the hepatic transferrin receptor 2 gene in mice leads to iron overload
Journal name Gastroenterology   Check publisher's open access policy
ISSN 0016-5085
Publication date 2007-01
Year available 2006
Sub-type Article (original research)
DOI 10.1053/j.gastro.2006.11.028
Volume 132
Issue 1
Start page 301
End page 310
Total pages 10
Place of publication Maryland Heights, MO, United States
Publisher W.B. Saunders Co.
Language eng
Formatted abstract
Background & Aims: Transferrin receptor 2 (TfR2) plays a key role in the regulation of iron metabolism. Mutations of TfR2 in humans cause type 3 hereditary hemochromatosis. Although highly expressed in liver, several studies have reported TfR2 expression in other tissues. To determine the contribution of liver expressed TfR2 in iron homeostasis, we have generated and characterized a liver-specific TfR2-knockout (KO) mouse.
Methods: Liver-specific TfR2-KO mice were generated by crossing TfR2-floxed mice with transgenic albumin-Cre mice. Tissue and serum from homozygous TfR2-floxed mice with and without albumin-Cre were analyzed. Serum transferrin saturation, hepatic, and splenic iron concentrations were determined. The expression of iron-related mRNA transcripts was analyzed by real-time PCR. Levels of the iron-related proteins TfR1, TfR2, ferritin, and prohepcidin were analyzed by immunoblotting.
Results: Liver-specific TfR2-KO mice develop significant iron overload comparable to complete TfR2-KO mice. At all ages studied, transferrin saturation, hepatic iron concentration, and hepatic ferritin were significantly elevated. Hepatic TfR2 mRNA and protein were absent in the livers of liver-specific TfR2-KO mice, and TfR1 expression was reduced consistent with liver iron loading. At 5 weeks of age, hepcidin1 mRNA, and prohepcidin protein were decreased in liver-specific TfR2-KO compared to control mice.
Conclusions: The significant iron loading and modulation of expression of iron-related genes in liver-specific TfR2-KO mice demonstrates that the liver is the primary site for TfR2 expression and activity and that liver-expressed TfR2 is required for the regulation of hepcidin1.
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Available online 18 November 2006

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Medicine Publications
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Citation counts: TR Web of Science Citation Count  Cited 67 times in Thomson Reuters Web of Science Article | Citations
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Created: Thu, 25 Nov 2010, 10:33:43 EST