Table 2.

Key recent mouse model studies of iron and/or Mn transport and trafficking.

Protein	Mouse model(s)	Metal(s) studied	Major finding(s)	Key reference (s)
DMT1	Intestine-specific Dmt1 KO	Fe, Mn	DMT1 is essential for intestinal iron absorption, but is not required for Mn absorption.	[1]
DMT1	Hepatocyte-specific Dmt1 KO	Fe	Hepatocyte DMT1 is dispensable for the uptake of plasma NTBI and iron loading of the liver.	[26]
DMT1	Hepatocyte-specific Dmt1 KO	Fe	Hepatocyte DMT1 is required for iron mobilization from the liver. In this process, DMT1 likely functions in the lysosome, where it transports iron from degraded ferritin into the cytosol.	[29]
SLC39A14	Slc39a14 KO, Hfe;Slc39a14 DKO, Hjv;Slc39a14 DKO	Fe	SLC39A14 is required for the uptake of plasma NTBI and iron loading of the liver (hepatocytes) and pancreas (acinar cells) in mouse models of genetic and dietary iron overload.	[5]
SLC39A14	Slc39a14 KO	Mn	SLC39A14 is required for the uptake of plasma Mn by the liver and pancreas and for gastrointestinal Mn excretion. Mn accumulates in the blood, brain, bone, and kidney.	[71–73]
SLC39A14	Intestine-specific Slc39a14 KO	Mn	Intestinal SLC39A14 localizes to the basolateral membrane of enterocytes, where it takes up Mn from the plasma to promote Mn elimination.	[75,85]
SLC39A8	Slc39a8 KO, Hepatocyte-specific Slc39a8 KO	Mn	SLC39A8 localizes to the hepatocyte apical membrane, where it reclaims Mn from the bile to protect against Mn deficiency.	[68]
SLC30A10	Slc30a10 KO	Mn	SLC30A10 deficiency results in marked increases in Mn levels in liver, blood, and brain, similar to human patients.	[58]
SLC30A10	Slc30a10 KO, Slc30a10-GFP, Hepatocyte-specific Slc30a10 KO, Enterocyte-specific Slc30a10 KO, Hepatocyte- and enterocyte-specific Slc30a10 DKO	Mn	SLC30A10 localizes to the hepatocyte apical membrane, where it exports Mn into bile, and to the duodenal enterocyte apical membrane, where it exports Mn into the lumen to promote Mn elimination. Combined Slc30a10 deficiency in the liver and enterocyte indicate that additional sites of SLC30A10 contribute to Mn homeostasis.	[62]
Ferroportin	Erythroblast-specific ferroportin KO	Fe	Erythrocyte ferroportin functions to export iron in mature red blood cells.	[41]
Ferroportin	Tmprss6 KO (hepcidin overexpressing), Intestine-specific ferroportin KO	Fe, Mn	Ferroportin plays a major role in iron, but not Mn, transport in vivo. Intestinal ferroportin is not required for Mn absorption.	[84]
PCBP1	Pcbp1 KO	Fe	PCBP1 in erythroid cells delivers iron to ferritin and is required for erythroid iron homeostasis.	[33]
Hephaestin, Ceruloplasmin	Heph KO, Cp KO, Heph;Cp DKO, Intestine-specific Heph; Cp DKO	Fe	Hephaestin and ceruloplasmin are not essential for intestinal iron absorption but are required for normal systemic iron distribution.	[21]