Divalent metal transporter, DMT1: a novel MRI reporter protein.
Manganese (Mn)-enhanced MRI (MEMRI) has found a growing number of applications in anatomical and functional imaging in small animals, based on the cellular uptake of Mn ions in the brain, heart, and other organs. Previous studies have relied on endogenous mechanisms of paramagnetic Mn ion uptake and enhancement. To genetically control MEMRI signals, we reverse engineered a major component of the molecular machinery involved in Mn uptake, the divalent metal transporter, DMT1. DMT1 provides positive cellular enhancement in a manner that is highly sensitive and dynamic, allowing greater spatial and temporal resolution for MRI compared to previously proposed MRI reporters such as ferritin. We characterized the MEMRI signal enhancement properties of DMT1-expressing cells, both in vitro and in vivo in mouse models of cancer and brain development. Our results show that DMT1 provides an effective genetic MRI reporter for a wide range of biological and preclinical imaging applications.
Kimmel Center for Biology and Medicine at the Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York, USA; Molecular Biophysics Graduate Program, New York University School of Medicine, New York, New York, USA.
Benjamin B
BB
Bartelle
Kamila U
KU
Szulc
Giselle A
GA
Suero-Abreu
Joe J
JJ
Rodriguez
Daniel H
DH
Turnbull
D000818:Animals; D001923:Brain Chemistry; D027682:Cation Transport Proteins / Q000032:analysis*; D066298:In Vitro Techniques; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese; D051379:Mice; D000099236:Solute Carrier Family 11, Member 2
D027682:Cation Transport Proteins; D008345:Manganese; D000099236:Solute Carrier Family 11, Member 2