Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk

Kumar, Loveleen, Michalczyk, Agnes, McKay, Jill, Ford, Dianne, Kambe, Taiho, Hudek, Lee, Varigios, George, Taylor, Philip E. and Ackland, M. Leigh 2015, Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk, Genes and nutrition, vol. 10, no. 38, pp. 487-502, doi: 10.1007/s12263-015-0487-x.

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Title Altered expression of two zinc transporters, SLC30A5 and SLC30A6, underlies a mammary gland disorder of reduced zinc secretion into milk
Author(s) Kumar, Loveleen
Michalczyk, AgnesORCID iD for Michalczyk, Agnes orcid.org/0000-0001-5716-0783
McKay, Jill
Ford, Dianne
Kambe, Taiho
Hudek, LeeORCID iD for Hudek, Lee orcid.org/0000-0002-5722-9346
Varigios, George
Taylor, Philip E.ORCID iD for Taylor, Philip E. orcid.org/0000-0002-4204-1893
Ackland, M. LeighORCID iD for Ackland, M. Leigh orcid.org/0000-0002-7474-6556
Journal name Genes and nutrition
Volume number 10
Issue number 38
Start page 487
End page 502
Total pages 16
Publisher Springer
Place of publication New York, N.Y.
Publication date 2015-09
ISSN 1555-8932
1865-3499
Keyword(s) Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
Nutrition & Dietetics
Zinc
Zinc transporters
Mammary
Neonatal zinc deficiency
DNA methylation
Lactation
LETHAL MILK
PREMATURE-INFANT
GENE-EXPRESSION
PRETERM INFANT
DEFICIENCY
CELLS
MUTATION
ACRODERMATITIS
PATHWAY
Summary Two cases of zinc deficiency in breastfed neonates were investigated where zinc levels in the mothers' milk were reduced by more than 75 % compared to normal. The objective of this study was to find the molecular basis of the maternal zinc deficiency condition. Significant reductions in mRNA expression and protein levels of the zinc transporters SLC30A5 and SLC30A6 were found in maternal tissue, suggesting a causal link to the zinc-deficient milk. Novel splice variants of the SLC30A6 transcript were detected. No modifications were found in coding regions, or in transcription binding sites of promoter regions or in 5' and 3' untranslated regions of both transporters in lymphoblasts and fibroblasts isolated from both mothers. Altered DNA methylation in SLC30A5 at two CpG sites was detected and may account for the reduced levels of SLC30A5 mRNA and protein in lymphoblasts. Reduced SLC30A6 mRNA and protein levels in lymphoblasts may be secondary to reduced SLC30A5 expression, as they function as a heterodimer in zinc transport. In conclusion, two cases of zinc deficiency are linked to low levels of the SLC30A5 and SLC30A6 zinc transporters. These two zinc transporters have not been previously associated with zinc deficiency in milk.
Language eng
DOI 10.1007/s12263-015-0487-x
Field of Research 111699 Medical Physiology not elsewhere classified
Socio Economic Objective 920114 Reproductive System and Disorders
HERDC Research category C1 Refereed article in a scholarly journal
Copyright notice ©2015, Springer
Persistent URL http://hdl.handle.net/10536/DRO/DU:30078504

Document type: Journal Article
Collection: School of Life and Environmental Sciences
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