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ZnT4‐null mice have impaired pubertal mammary gland development resulting in lactation defects
Author(s) -
McCormick Nicholas,
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.lb286
Subject(s) - lactation , stromal cell , mammary gland , biology , endocrinology , medicine , microbiology and biotechnology , duct (anatomy) , cancer research , anatomy , pregnancy , genetics , cancer , breast cancer
Proper mammary gland (MG) development is needed to provide milk of optimal quality and quantity for the growing infant. MG development requires communication between stromal and epithelial tissue. It consists of epithelial proliferation and invasion into the mammary fat pad during puberty, and extensive secondary branching and lobular‐alveolar differentiation during reproduction. Many of these cellular processes are zinc (Zn) dependent. ZnT4 provides Zn for vital mammary cell functions. ZnT4‐null mice have smaller and functionally impaired MGs. We hypothesized that ZnT4 provides Zn for processes that are critical for optimal MG development. During lactation, ZnT4‐null mice had ~30% fewer alveoli and sparse ductal architecture. However, the ducts and alveoli were well‐organized, patent and did not accumulate lipid droplets. During development, increased proliferating and apoptotic cells in stromal tissue were noted, suggesting greater stromal turnover in ZnT4‐null MGs. Moreover, ZnT4‐null mice had comparable primary duct invasion but less secondary branching. This suggests that impaired MG function during lactation results from impaired pubertal development and not defects in differentiation during reproduction, and implicates ZnT4‐mediated Zn transport as a critical regulator of optimal MG development. Grant Funding Source: Supported by NIH R01 HD058614 to SLK.