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ZnT2‐null mice have distinct morphological defects in the mammary gland that impair development and function
Author(s) -
Lee Sooyeon,
Hennigar Stephen R,
Alam Samina,
Kelleher Shan L
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.733.7
Subject(s) - lactation , medicine , endocrinology , litter , mammary gland , biology , secretion , chemistry , andrology , pregnancy , ecology , genetics , cancer , breast cancer
Women with genetic variation in ZnT2 have ~75% lower milk zinc (Zn) levels during lactation. ZnT2 imports Zn into mitochondria and secretory vesicles in mammary epithelial cells (MECs), which suggests that ZnT2 plays critical roles in mammary gland (MG) function and Zn secretion into milk. We used female ZnT2‐null (KO) mice to explore effects on MG function. While plasma Zn was similar, MG Zn content was significantly lower in adult KO compared with wild‐type (WT) mice (5.6 ± 0.5 vs 11.4 ± 0.9 μg/g; p<0.05). KO MGs had irregular ductal branching, tightly clustered alveoli and greater collagen deposition around collapsed ducts. MG Zn content increased in both genotypes during lactation, but metallothionein expression was ~7 fold higher (p<0.05) in KO compared with WT mice, suggesting Zn sequestration. Lipid accumulation was noted in MECs and the alveolar lumen of KO mice, suggesting secretion defects. Mice were bred and although pregnancy rate, litter size and weight were similar, KO mice had fewer litters surviving past d1 compared with WT mice (41% ± 46 vs 96% ± 6.1; p<0.05). Interestingly, pups from KO dams had greater total body Zn content compared with WT pups (77.7 ± 3.2 vs 56.9 ± 7.4 μg/g; p<0.05), suggesting Zn transfer in utero was enhanced. Our data implicate ZnT2 as a critical mediator of MG development and function and suggest that women with genetic variation in ZnT2 may have substantial lactational defects beyond the inability to transfer sufficient Zn into milk. Supported by NIH # HD058614 to SLK.