IFIBYNE   05513
INSTITUTO DE FISIOLOGIA, BIOLOGIA MOLECULAR Y NEUROCIENCIAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Reduction of tristetraprolin expression alters lactation in conditional KO mice
Autor/es:
GODDIO MV; MEISS RP; PEREZ CUERVO L; LACUNZA E; TOCCI J; GIACCOLLO A; VEGGETI M; ABBA MC; EDITH KORDON
Reunión:
Congreso; Gordon Research Conference on Mammary Gland; 2013
Resumen:
Mammary gland development is a complex, multistep process. From pregnancy to lactation, lobulo-alveolar growth is followed by the complete differentiation of mammary epithelium, 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 invasiveness-associated genes. Our previous results showed that TTP expression is associated to differentiation of normal and neoplastic mammary cells. In order to determine whether this protein plays a relevant physiological role during lactation, we proceeded to analyze the consequences of deleting TTP specifically 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, after delivery, bi-transgenic animals showed smaller glands with lower content of milk. In addition, signs of involution, as apoptotic nuclei, expression of inflammatory cytokines and metalloproteases appeared earlier these mice compared to loxP-TTP controls. These observations suggest that TTP would contribute to lactation maintenance and its activity, as tumor suppressor protein, might be associated to its ability to prevent involution-associated events in the mammary gland.