Loss of tristetraprolin (TTP) expression alters lactation in conditional KO mice

GODDIO MV; PEREZ-CUERVO L 1; LACUNZA E; TOCCI J; GIACOLLO A; VEGGETTI; ABBA M; KORDON E

Simposio; SISTAM 2012 “The Second South American Spring Symposium in Signal Transduction and Molecular Medicine”; 2012

Mammary gland development is a complex, multistep process. From pregnancy to lactation, lobulo-alveolar growth is followed by the complete differentiation of mammary epitheliu m, which allows the production and secretion of milk proteins. At weaning, a rapid switch from survival to death signaling occurs, leading to involution, which involves extensive remodeling and an innate immune response in the tissue. Tristetraprolin (TTP) is a RNA-binding protein that inhibits the expression of pro- inflammatory cytokines and invasivene ss-associated genes. Our results show that TTP expression is associat ed to differentiation of normal and neoplastic mammary cells. In order to determine whether this protein play a relevant physiological role during lactation, we proceeded to analyze the consequences of deleting TTP specif ically in the mammary gland during lactation. To that goal, WAP-Cre recombinase transgenic mice, in which the enzyme is expressed uniquely in the lactating mammary tissue, were crossed with lox-P TTP transgenic animals. By PCR we detected the bi- transgenic animals and the specific deletion of TTP in their mammary glands after parturition. Then, we analyzed the mammary tissue at different times after parturition and after separating the pups from their mothers (forced involution). We found that double transgenic animals showed smaller glands after delivery with lower content of milk.Hemathoxylin-eosin staining revealed t hat signs of involution, as apoptotic nuclei, appeared earlier in bi-transgenic animals, suggesting that TTP is contributing to maintenance of lactation. More studies are underway to determine how TTP loss affects the pattern of expression and activation of different proteins associated to lactation.