Hepcidin antimicrobial peptide serves as the master regulator of iron homeostasis by limiting iron entry into the plasma from macrophages, intestinal enterocytes and other cells through binding to the iron-export protein ferroportin, and facilitating its internalization and degradation. Hepcidin antimicrobial peptide is induced by inflammation and is involved in anemia of chronic diseases and inflammation. These transgenic mice express mouse Hamp under control of the tetO, tetracycline-responsive regulatory element promoter. When crossed with a tTA strain, Hamp expression can be temporally regulated by doxycycline administration. For example, when TRE.Hepc1 mice are bred to a strain expressing tTA in liver, such as Stock No. 003563, the resulting double transgenic mice overexpress Hamp in the liver, resulting in hypoferremia, hypochromic and microcytic anemia, as well as anemia of inflammation. Doxycycline or tetracycline administration is expected to repress expression of the transgene in the double mutant mice.
Mice hemizygous for the TRE.Hepc1 transgene are viable, fertile, normal in size and do not display any gross physical or behavioral abnormalities. The Donating Investigator reports that putative homozygotes are viable and fertile.
The Donating Investigator notes that there can be a wide range of phenotypic expression in double mutant mice, which may be due to the tTA transgene used or regulation of the endogenous hepcidin.
