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The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border.

Publication ,  Journal Article
Canonne-Hergaux, F; Fleming, MD; Levy, JE; Gauthier, S; Ralph, T; Picard, V; Andrews, NC; Gros, P
Published in: Blood
December 1, 2000

Microcytic anemia (mk) mice and Belgrade (b) rats are severely iron deficient because of impaired intestinal iron absorption and defective iron metabolism in peripheral tissues. Both animals carry a glycine to arginine substitution at position 185 in the iron transporter known as Nramp2/DMT1 (divalent metal transporter 1). DMT1 messenger RNA (mRNA) and protein expression has been examined in the gastrointestinal tract of mk mice. Northern blot analysis indicates that, by comparison to mk/+ heterozygotes, mk/mk homozygotes show a dramatic increase in the level of DMT1 mRNA in the duodenum. This increase in RNA expression is paralleled by a concomitant increase of the 100-kd DMT1 isoform I protein expression in the duodenum. Immunohistochemical analyses show that, as for normal mice on a low-iron diet, DMT1 expression in enterocytes of mk/mk mice is restricted to the duodenum. However, and in contrast to normal enterocytes, little if any expression of DMT1 is seen at the apical membrane in mk/mk mice. These results suggest that the G185R mutation, which was shown to impair the transport properties of DMT1, also affects the membrane targeting of the protein in mk/mk enterocytes. This loss of function of DMT1 is paralleled by a dramatic increase in expression of the defective protein in mk/mk mice. This is consistent with a feedback regulation of DMT1 expression by iron stores. (Blood. 2000;96:3964-3970)

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

December 1, 2000

Volume

96

Issue

12

Start / End Page

3964 / 3970

Location

United States

Related Subject Headings

  • Tissue Distribution
  • RNA, Messenger
  • Microvilli
  • Mice, Mutant Strains
  • Mice
  • Membrane Proteins
  • Iron-Binding Proteins
  • Iron, Dietary
  • Immunology
  • Immunohistochemistry
 

Citation

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MLA
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Canonne-Hergaux, F., Fleming, M. D., Levy, J. E., Gauthier, S., Ralph, T., Picard, V., … Gros, P. (2000). The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border. Blood, 96(12), 3964–3970.
Canonne-Hergaux, F., M. D. Fleming, J. E. Levy, S. Gauthier, T. Ralph, V. Picard, N. C. Andrews, and P. Gros. “The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border.Blood 96, no. 12 (December 1, 2000): 3964–70.
Canonne-Hergaux F, Fleming MD, Levy JE, Gauthier S, Ralph T, Picard V, et al. The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border. Blood. 2000 Dec 1;96(12):3964–70.
Canonne-Hergaux F, Fleming MD, Levy JE, Gauthier S, Ralph T, Picard V, Andrews NC, Gros P. The Nramp2/DMT1 iron transporter is induced in the duodenum of microcytic anemia mk mice but is not properly targeted to the intestinal brush border. Blood. 2000 Dec 1;96(12):3964–3970.

Published In

Blood

ISSN

0006-4971

Publication Date

December 1, 2000

Volume

96

Issue

12

Start / End Page

3964 / 3970

Location

United States

Related Subject Headings

  • Tissue Distribution
  • RNA, Messenger
  • Microvilli
  • Mice, Mutant Strains
  • Mice
  • Membrane Proteins
  • Iron-Binding Proteins
  • Iron, Dietary
  • Immunology
  • Immunohistochemistry