First phenotypic description of transferrin receptor 2 knockout mouse, and the role of hepcidin.
BACKGROUND
Transferrin receptor 2 (TfR2) is a key molecule involved in the regulation of iron homeostasis. Mutations in humans cause type 3 haemochromatosis and a targeted mutation in mice leads to iron overload with a similar phenotype. We have previously described the generation of a complete TfR2-knockout (KO) mouse.


OBJECTIVE
The aims of this study were to determine the phenotype and analyse expression of iron related molecules in the liver, duodenum, and spleen of homozygous TfR2-KO, heterozygous, and wild-type mice.


METHODS
Serum and tissue iron levels were determined in 10 week old male mice. Expression of iron related mRNA transcripts were analysed in the liver, duodenum, and spleen using real time polymerase chain reaction. Expression of iron related proteins in the liver were analysed by immunoblotting and immunohistochemistry.


RESULTS
Homozygous TfR2-KO mice had no TfR2 protein expression and developed significant iron overload typical of TfR2 associated haemochromatosis. In the liver of TfR2-KO mice there was no upregulation of hepcidin mRNA or prohepcidin protein in response to iron loading.


CONCLUSIONS
Our results suggest that TfR2 is required for iron regulated expression of hepcidin and is involved in a pathway related to Hfe and hemojuvelin.
Wallace
D F
DF
The Membrane Transport Laboratory, Cancer and Cell Biology Division, The Queensland Institute of Medical Research, Brisbane, Queensland, Australia.
Summerville
L
L
Lusby
P E
PE
Subramaniam
V N
VN
D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis* / Q000235:genetics; D004386:Duodenum / Q000378:metabolism; D005786:Gene Expression Regulation; D064451:Hepcidins; D007124:Immunoenzyme Techniques; D019190:Iron Overload / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D011990:Receptors, Transferrin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013154:Spleen / Q000378:metabolism
D023181:Antimicrobial Cationic Peptides; C578702:HAMP protein, human; C579599:Hamp protein, mouse; D064451:Hepcidins; D012333:RNA, Messenger; D011990:Receptors, Transferrin; C503641:TFR2 protein, mouse