Generation and characterization of transgenic mice hyper-expressing melanoma tumour antigen p97 (Melanotransferrin): No overt alteration in phenotype

Abstract

Melanotransferrin (MTf) is a transferrin homologue that binds iron (Fe) through a high affinity Fe-binding site. MTf has been implicated in diverse processes, e.g., iron metabolism, plasminogen activation, eosinophil differentiation and cancer cell migration, proliferation and tumourigenesis. Our previous studies using a knockout mouse demonstrated that MTf does not have an essential function in Fe metabolism (E.O. Sekyere, L.L. Dunn, Y.S. Rahmanto, D.R. Richardson, Role of melanotransferrin in iron metabolism: studies using targeted gene disruption in vivo, Blood 107 (2006) 2599–2601). However, it does play a role in melanoma cell proliferation and tumourigenesis. In this investigation, we report generation and characterization of transgenic mice bearing the MTf gene (MTfTg) produced via lentiviral delivery. In MTfTg mice, MTf mRNA and protein were hyper-expressed in tissues compared to control mice. These animals exhibited no gross morphological, histological, nor Fe status changes. The MTfTg mice were also born in accordance with classical Mendelian ratios. However, hyper-expression of MTf leads to a mild, but significant decrease in erythrocyte count. This animal provides a novel MTf hyper-expression transgenic model for further investigating the biological function(s) of MTf.