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Sooyeon Lee, Yandong Zhou, Donald L Gill, Shannon L Kelleher
SLC30A2 encodes a zinc (Zn) transporter (ZnT2) that imports Zn into vesicles in highly-specialized secretory cells. Numerous mutations and non-synonymous variants in ZnT2 have been reported in humans and in breastfeeding women; ZnT2 variants are associated with abnormally low milk Zn levels and can lead to severe infantile Zn deficiency. However, ZnT2-null mice have profound defects in mammary epithelial cell (MEC) polarity and vesicle secretion, indicating that normal ZnT2 function is critical for MEC function...
February 23, 2018: Scientific Reports
Yarden Golan, Taiho Kambe, Yehuda G Assaraf
Breast milk is the optimal nutrient mix for infants until the age of 6 months. However, in some cases, due to genetic alterations as well as nutrient deficiencies in nursing mothers, infants may suffer from inadequate levels of micronutrients upon exclusive breastfeeding. In this respect, transient neonatal zinc deficiency (TNZD) is caused by loss-of-function mutations in the zinc transporter SLC30A2/ZnT2 gene, resulting in poor secretion of zinc into the breast milk. Consequently, infants exclusively breastfed with zinc-deficient breast milk develop severe zinc deficiency...
October 18, 2017: Metallomics: Integrated Biometal Science
Hui M Liew, Colin W Tan, Clement K M Ho, Jade N Chee, Mark J A Koh
This is a case report of a 4-month-old full-term, fully breastfed boy who presented with a persistent periorificial and groin rash associated with poor weight gain and irritability. His serum zinc level was low. The mother's breast milk zinc level was found to be low despite her serum zinc levels being normal, confirming the diagnosis of transient neonatal zinc deficiency. Mutational analysis revealed a novel mutation in the mother's SLC30A2 gene, which encodes a zinc transporter expressed in mammary gland epithelial cells...
March 2017: Pediatric Dermatology
Jianping Jiang, Yahui Gao, Yali Hou, Wenhui Li, Shengli Zhang, Qin Zhang, Dongxiao Sun
The use of whole-genome resequencing to obtain more information on genetic variation could produce a range of benefits for the dairy cattle industry, especially with regard to increasing milk production and improving milk composition. In this study, we sequenced the genomes of eight Holstein bulls from four half- or full-sib families, with high and low estimated breeding values (EBVs) of milk protein percentage and fat percentage at an average effective depth of 10×, using Illumina sequencing. Over 0.9 million nonredundant short insertions and deletions (indels) [1-49 base pairs (bp)] were obtained...
2016: PloS One
Stephen R Hennigar, Alyssa M Kelley, James P McClung
Zinc is an essential nutrient for humans; however, a sensitive biomarker to assess zinc status has not been identified. The objective of this systematic review was to compile and assess studies that determined zinc transporter and/or metallothionein expression in various blood cell types and to determine their reliability and sensitivity to changes in dietary zinc. Sixteen studies were identified that determined the expression of zrt-, irt-like protein (ZIP) 1 [solute carrier family (SLC) 39A1], ZIP3 (SLC39A3), ZIP5 (SLC39A5), ZIP6 (SLC39A6), ZIP7 (SLC39A7), ZIP8 (SLC39A8), ZIP10 (SLC39A10), ZIP14 (SLC39A14), zinc transporter (ZnT)1 (SLC30A1), ZnT2 (SLC30A2), ZnT4 (SLC30A4), ZnT5 (SLC30A5), ZnT6 (SLC30A6), ZnT7 (SLC30A7), ZnT9 (SLC30A9), and/or metallothionein in various blood cells isolated from healthy adult men and women in response to zinc supplementation or depletion...
July 2016: Advances in Nutrition
Samina Alam, Stephen R Hennigar, Carla Gallagher, David I Soybel, Shannon L Kelleher
No abstract text is available yet for this article.
December 2016: Journal of Mammary Gland Biology and Neoplasia
Naoya Itsumura, Yoshie Kibihara, Kazuhisa Fukue, Akiko Miyata, Kenji Fukushima, Risa Tamagawa-Mineoka, Norito Katoh, Yukina Nishito, Riko Ishida, Hiroshi Narita, Hiroko Kodama, Taiho Kambe
BACKGROUND: Infants are vulnerable to zinc deficiency. Thus, abnormally low breast milk zinc levels cause transient neonatal zinc deficiency (TNZD) in breast-fed infants. TNZD has been considered to be rare because of a paucity of citations in the published literature. However, recent studies of affected mothers identified four missense mutations in the solute carrier family 30 member 2 gene (SLC30A2), which encodes the zinc transporter, ZnT2. METHODS: Genetic analyses of SLC30A2/ZnT2 in three Japanese mothers secreting low-zinc milk (whose infants developed TNZD) were performed...
October 2016: Pediatric Research
Kathryn M McRae, Barbara Good, James P Hanrahan, Matthew S McCabe, Paul Cormican, Torres Sweeney, Mary J O'Connell, Orla M Keane
Gastrointestinal nematodes are a serious cause of morbidity and mortality in grazing ruminants. The major ovine defence mechanism is acquired immunity, with protective immunity developing over time in response to infection. Nematode resistance varies both within and between breeds and is moderately heritable. A detailed understanding of the genes and mechanisms involved in protective immunity, and the factors that regulate this response, is required to aid both future breeding strategies and the development of effective and sustainable nematode control methods...
July 15, 2016: Veterinary Parasitology
Samina Alam, Stephen R Hennigar, Carla Gallagher, David I Soybel, Shannon L Kelleher
The zinc (Zn) transporter ZnT2 (SLC30A2) is expressed in specialized secretory cells including breast, pancreas and prostate, and imports Zn into mitochondria and vesicles. Mutations in SLC30A2 substantially reduce milk Zn concentration ([Zn]) and cause severe Zn deficiency in exclusively breastfed infants. Recent studies show that ZnT2-null mice have low milk [Zn], in addition to profound defects in mammary gland function during lactation. Here, we used breast milk [Zn] to identify novel non-synonymous ZnT2 variants in a population of lactating women...
December 2015: Journal of Mammary Gland Biology and Neoplasia
Inkie J A Evers-van Gogh, Sheril Alex, Rinke Stienstra, Arjan B Brenkman, Sander Kersten, Eric Kalkhoven
Regular exercise has emerged as one of the best therapeutic strategies to prevent and treat type-2-diabetes. Exercise-induced changes in the muscle secretome, consisting of myokines and metabolites, may underlie the inter-organ communication between muscle and other organs. To investigate this crosstalk, we developed an in vitro system in which mouse C2C12 myotubes underwent electric pulse stimulation (EPS) to induce contraction. Subsequently the effects of EPS-conditioned media (EPS-CM) on hepatocytes were investigated...
2015: Scientific Reports
Sooyeon Lee, Stephen R Hennigar, Samina Alam, Keigo Nishida, Shannon L Kelleher
The zinc transporter ZnT2 (SLC30A2) imports zinc into vesicles in secreting mammary epithelial cells (MECs) and is critical for zinc efflux into milk during lactation. Recent studies show that ZnT2 also imports zinc into mitochondria and is expressed in the non-lactating mammary gland and non-secreting MECs, highlighting the importance of ZnT2 in general mammary gland biology. In this study we used nulliparous and lactating ZnT2-null mice and characterized the consequences on mammary gland development, function during lactation, and milk composition...
May 22, 2015: Journal of Biological Chemistry
Yanliang Jiang, Songhao Zhang, Shuaisheng Feng, Jinsheng Sun, Peng Xu
BACKGROUND: Zinc is an essential trace element in organisms, which serves as a cofactor for hundreds of enzymes that are involved in many pivotal biological processes including growth, development, reproduction and immunity. Therefore, the homeostasis of zinc in the cell is fundamental. The zinc transporter gene family is a large gene family that encodes proteins which regulate the movement of zinc across cellular and intracellular membranes. However, studies on teleost zinc transporters are mainly limited to model species...
2014: PloS One
Monika Schweigel-Röntgen
The solute carriers families 30 (SLC30; ZnT), 39 (SLC39; ZIP), and 31 (SLC31; CTR) are involved in the essential maintenance of cellular zinc (Zn²⁺) and copper (Cu²⁺) homeostasis, respectively. ZnTs mediate Zn²⁺ extrusion from cells (SLC30A1) or transport Zn²⁺ into organelles and secretory vesicles/granules (SLC30A2-SLC30A8). SLC39 family members are predominantly localized to the cell membrane where they perform Zn²⁺ uptake and increase the availability of cytosolic Zn²⁺. SLC39A1 is ubiquitously expressed, whereas other ZIP transporters (e...
2014: Current Topics in Membranes
Miguel Lova Navarro, Angel Vera Casaño, Carmen Benito López, María D Fernández Ballesteros, Daniel J Godoy Díaz, Antonio Crespo Erchiga, Santiago Romero Brufau
Transient neonatal zinc deficiency (TNZD) has a clinical presentation similar to that of acrodermatitis enteropathica but is caused by a low zinc concentration in maternal breast milk. TNZD becomes clinically evident during breastfeeding and is resolved by weaning and the introduction of complementary nutrition. We present a 4-month-old girl with TNZD due to a new autosomal dominant mutation (663delC) in the maternal SLC30A2 gene not previously described in the literature.
March 2014: Pediatric Dermatology
Maria Consolata Miletta, Andreas Bieri, Kristin Kernland, Martin H Schöni, Vibor Petkovic, Christa E Flück, Andrée Eblé, Primus E Mullis
Suboptimal dietary zinc (Zn(2+)) intake is increasingly appreciated as an important public health issue. Zn(2+) is an essential mineral, and infants are particularly vulnerable to Zn(2+) deficiency, as they require large amounts of Zn(2+) for their normal growth and development. Although term infants are born with an important hepatic Zn(2+) storage, adequate Zn(2+) nutrition of infants mostly depends on breast milk or formula feeding, which contains an adequate amount of Zn(2+) to meet the infants' requirements...
2013: International Journal of Endocrinology
Lena Martin, Ulrike Lodemann, Angelika Bondzio, Eva-Maria Gefeller, Wilfried Vahjen, Jörg Rudolf Aschenbach, Jürgen Zentek, Robert Pieper
High dietary zinc concentrations are used to prevent or treat diarrhea in piglets and humans, but long-term adaptation to high zinc supply has yet not been assessed. Intestinal zinc uptake is facilitated through members of zinc transporter families SLC30 (ZnT) and SLC39 (ZIP). Whereas in rodents, regulation of zinc homeostasis at low or adequate zinc supply has been described, such mechanisms are unclear in piglets. A total of 54 piglets were fed diets containing 57 [low dietary zinc (LZn)], 164 [normal dietary zinc (NZn)], or 2425 [high dietary zinc (HZn)] mg/kg dry matter zinc...
August 2013: Journal of Nutrition
Naoya Itsumura, Yasuji Inamo, Fumiko Okazaki, Fumie Teranishi, Hiroshi Narita, Taiho Kambe, Hiroko Kodama
Zinc concentrations in breast milk are considerably higher than those of the maternal serum, to meet the infant's requirements for normal growth and development. Thus, effective mechanisms ensuring secretion of large amounts of zinc into the milk operate in mammary epithelial cells during lactation. ZnT2 was recently found to play an essential role in the secretion of zinc into milk. Heterozygous mutations of human ZnT2 (hZnT2), including H54R and G87R, in mothers result in low (>75% reduction) secretion of zinc into the breast milk, and infants fed on the milk develop transient neonatal zinc deficiency...
2013: PloS One
R S Lisle, K Anthony, M A Randall, F J Diaz
Zinc increases in the oocyte during maturation and is required for progression and completion of meiosis. The objective of this study was to determine whether cumulus cells regulate the levels of free intracellular zinc in the oocyte during maturation. In the cumulus-oocyte complex (COC) the relative level of free intracellular zinc was almost fourfold higher in cumulus cells compared with the resident germinal vesicle-stage oocyte. Removal of cumulus cells caused a fourfold increase in intracellular zinc in the oocyte by 1 h after cumulus cell removal, but subsequent coculture of denuded oocytes with COC decreased free intracellular zinc in the oocyte by 65%...
April 1, 2013: Reproduction: the Official Journal of the Society for the Study of Fertility
Inbal Lasry, Young Ah Seo, Hadas Ityel, Nechama Shalva, Ben Pode-Shakked, Fabian Glaser, Bluma Berman, Igor Berezovsky, Alexander Goncearenco, Aharon Klar, Jacob Levy, Yair Anikster, Shannon L Kelleher, Yehuda G Assaraf
Zinc is an essential mineral, and infants are particularly vulnerable to zinc deficiency as they require large amounts of zinc for their normal growth and development. We have recently described the first loss-of-function mutation (H54R) in the zinc transporter ZnT-2 (SLC30A2) in mothers with infants harboring transient neonatal zinc deficiency (TNZD). Here we identified and characterized a novel heterozygous G87R ZnT-2 mutation in two unrelated Ashkenazi Jewish mothers with infants displaying TNZD. Transient transfection of G87R ZnT-2 resulted in endoplasmic reticulum-Golgi retention, whereas the WT transporter properly localized to intracellular secretory vesicles in HC11 and MCF-7 cells...
August 24, 2012: Journal of Biological Chemistry
Linxi Qian, Bei Wang, Ning Tang, Weili Zhang, Wei Cai
The variability of breast-milk zinc concentration is high among breastfeeding women, and it is known to be independent of dietary zinc intake. As a result, transient neonatal zinc deficiency is not rare in the breastfed infants due to low milk zinc concentration in their breastfeeding mothers. Up to now, SLC30A2 has been documented the only candidate gene showing correlation with human milk zinc trait. In this study, 750 breastfeeding women were recruited and 10ml foremilk was collected on 42nd postpartum day...
August 2012: Early Human Development
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