Akrodermatitis enteropathica ? eine Zinkstoffwechselst�rung mit Zinkmalabsorption

Lombeck, I.; Schnippering, Holger; Kasperek, K.; Ritzl, F.; Kästner, H; Feinendegen, L. E.; Bremer, H. J.

doi:10.1007/bf00439007

Cited by 44 publications

(18 citation statements)

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“…This autosomal recessive disorder causes classic symptoms of zinc deficiency (3), such as dermatological lesions, changes in the gastric mucosa associated with digestive system problems, lack of weight gain, and immune and reproductive problems (4 -8). Remarkably, these symptoms can be ameliorated by dietary zinc supplement (4, 6, 9 -11), consistent with the finding of reduced, but not eliminated, uptake of 65 Zn by the intestine from AE patients (12,13), and the reduced uptake and total content of zinc in AE fibroblasts (14,15). Recent genetic mapping localized the AE gene to chromosome 8q24.3 (16) and led to its identification as a member of the ZIP superfamily (17,18).…”

supporting

confidence: 72%

The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice

Dufner-Beattie

Wang

Kuo

et al. 2003

Journal of Biological Chemistry

266

297

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The human ZIP4 gene (SLC39A4) is a candidate for the genetic disorder of zinc metabolism acrodermatitis enteropathica. To understand its role in zinc homeostasis, we examined the function and expression of mouse ZIP4. This gene encodes a well conserved eight-transmembrane protein that can specifically increase the influx of zinc into transfected cells. Expression of this gene is robust in tissues involved in nutrient uptake, such as the intestines and embryonic visceral yolk sac, and is dynamically regulated by zinc. Dietary zinc deficiency causes a marked increase in the accumulation of ZIP4 mRNA in these tissues, whereas injection of zinc or increasing zinc content of the diet rapidly reduces its abundance. Zinc can also regulate the accumulation of ZIP4 protein at the apical surface of enterocytes and visceral endoderm cells. These results provide compelling evidence that ZIP4 is a zinc transporter that plays an important role in zinc homeostasis, a process that is defective in acrodermatitis enteropathica in humans.A long recognized disease of zinc metabolism is the human genetic disorder acrodermatitis enteropathica (AE) 1 (1, 2). This autosomal recessive disorder causes classic symptoms of zinc deficiency (3), such as dermatological lesions, changes in the gastric mucosa associated with digestive system problems, lack of weight gain, and immune and reproductive problems (4 -8). Remarkably, these symptoms can be ameliorated by dietary zinc supplement (4, 6, 9 -11), consistent with the finding of reduced, but not eliminated, uptake of 65 Zn by the intestine from AE patients (12, 13), and the reduced uptake and total content of zinc in AE fibroblasts (14,15). Recent genetic mapping localized the AE gene to chromosome 8q24.3 (16) and led to its identification as a member of the ZIP superfamily (17, 18). That gene was named hZIP4 (the Human Genome Organization Nomenclature Committee named this gene SLC39A4).ZIP4 was found to be expressed in enterocytes and to reside in the plasma membrane. Mutations in hZIP4 were detected in AE patients (17, 18), strongly suggesting that they cause this genetic disorder.The recently identified ZIP superfamily of metal ion uptake transporters (19,20) are found in all eukaryotes, and many of its members mediate zinc uptake. In yeast, ZRT1 encodes the high affinity zinc transporter, and ZRT2 encodes the low affinity zinc transport system. The Arabidopsis iron-regulated transporter gene (IRT1) encodes a metal transporter that has remarkable sequence similarity with the yeast ZRTs and with other Arabidopsis zinc transporters (19, 21). Thus, the acronym ZIP was adopted to reflect ZRT/IRT-related proteins. Many members of the ZIP gene superfamily have now been detected based on sequence homology with yeast and Arabidopsis ZIP genes (22, 23). The ZIP proteins typically have eight membrane-spanning domains, and spanning domain four contains fully conserved histidyl and glycyl residues in an amphipathic ␣-helix. These proteins also often have a histidine-rich intracellular loop between s...

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supporting

confidence: 72%

The Acrodermatitis Enteropathica Gene ZIP4 Encodes a Tissue-specific, Zinc-regulated Zinc Transporter in Mice

Dufner-Beattie

Wang

Kuo

et al. 2003

Journal of Biological Chemistry

266

297

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“…The intestinal absorption of 65Zn by young patients with Acrodermatitis enteropathica is reduced (Lombeck et al, 1975;Weissmann et al, 1979). Surprisingly in the light of clinical experience this defect was not shown in adult patients (Weissmann et al, 1979).…”

Section: Pathogenesismentioning

confidence: 97%

Acrodermatitis enteropathica

Aggett¹

1983

J of Inher Metab Disea

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“…There have been several attempts to administer zinc orally: zinc as partate [5], zinc oxide [9], zinc gluconate [II] and zinc sulfate have been pro posed [7,8,12], With the latter compound the clinical improvement is rapid and simultaneously the serum levels of zinc become normal.…”

Section: Discussionmentioning

confidence: 99%