Transgenic Mice Expressing Recombinant Human Protein C Exhibit Defects in Lactation and Impaired Mammary Gland Development

摘要: To determine if the production of recombinant human protein C (rHPC) could be increased in milk, we created two lines mice homozygous for mouse whey acidic (WAP)/human (HPC) transgene. Females both had normal growth, activity and fertility, but failed to lactate normally were unable raise litters. Histological analyses mammary glands from lactating females showed barely distended alveoli filled with dense-staining milk. Epithelial cells within these distinct, centrally located nuclei contained intracellular lipid droplets. Hemizygous animals derived able raised sized Northern blot analysis that 6.4 (6.4H) line expressed transgene at higher levels then corresponding hemizygous (6.4) animals, 4.2 (4.2H) lower than line. The 6.4H also rHPC milk as revealed by western analysis. 4.2H, 6.4, decreased and/or delayed expression WAP, β-casein, α-lactalbumin mRNA's compared wild type during lactogenesis. mRNA β-casein α-lactalbumin, or WAP Elevated some proteins detected transgenic mice. From results, it is concluded induced a lactational phenotype involves abnormal morphological, biochemical, functional differentiation epithelial cells. However, induction this does not appear directly related level expression, thus suggesting basis may involve secondary, rather primary, effects on gland development.