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Analysis of zinc transporter, hZnT4 (Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk

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Abstract

Zinc deficiency, causing impaired growth and development, may have a nutritional or genetic basis. We investigated two cases of inherited zinc deficiency found in breast-fed neonates, caused by low levels of zinc in the maternal milk. This condition is different from acrodermatitis enteropathica but has similarities to the "lethal milk" mouse, where low levels of zinc in the milk of lactating dams leads to zinc deficiency in pups. The mouse disorder has been attributed to a defect in the ZnT4 gene. Little is known about the expression of the human orthologue, hZnT4 (Slc30A4). Sequence analysis of cDNA, real-time PCR and Western blot analysis of hZnT4, carried out on control cells and cells from unrelated mothers of two infants with zinc deficiency, showed no differences. The hZnT4 gene was highly expressed in mouthwash buccal cells compared with lymphoblasts and fibroblasts. The hZnT4 protein did not co-localise with intracellular free zinc pools, suggesting that hZnT4 is not involved in transport of zinc into vesicles destined for secretion into milk. This observation, combined with phenotypic differences between the "lethal milk" mouse and the human disorder, suggests that the "lethal milk" mouse is not the corresponding model for the human zinc deficiency condition.

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Acknowledgements

We thank Dr Sharon La Fontaine for her very constructive comments during the preparation of the manuscript. This study was supported by funding from the Australian Research Council to M.L.A..

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Authors and Affiliations

  1. Centre for Cellular and Molecular Biology, School of Biological and Chemical Sciences, Deakin University, Burwood Campus, 221 Burwood Highway, 3125, Burwood, Victoria, Australia

    Agnes Michalczyk, Rachael C. Blomeley & M. Leigh Ackland

  2. Department of Dermatology, Royal Children's Hospital, Australia

    George Varigos

  3. Department of Gastroenterology and Clinical Nutrition, Royal Children's Hospital, Australia

    Anthony Catto-Smith

Authors
  1. Agnes Michalczyk
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  2. George Varigos
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  3. Anthony Catto-Smith
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  4. Rachael C. Blomeley
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  5. M. Leigh Ackland
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Correspondence to M. Leigh Ackland.

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Michalczyk, A., Varigos, G., Catto-Smith, A. et al. Analysis of zinc transporter, hZnT4 (Slc30A4), gene expression in a mammary gland disorder leading to reduced zinc secretion into milk. Hum Genet 113, 202–210 (2003). https://doi.org/10.1007/s00439-003-0952-2

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  • DOI: https://doi.org/10.1007/s00439-003-0952-2

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