proteins which are not normally secreted from the cells but act as chaperones, aiding protein folding. Their up-regulation is typically associated with ER stress [31, 32, 33] . This suggests that the lack of a-casein protein in mammary epithelial cells induces ER stress. Analysis of gene expression rates of grp78, grp94 and PDIA6 confirms that all three genes are significantly up-regulated in tissue samples of a-casein deficient mice with respect to control mice and heterozygous mice (Fig. 4d) . In contrast, another protein often upregulated under conditions of ER stress, REDD1 [34] is not significantly regulated by the absence of a-casein (Fig. 4d) , Several other protein bands with apparent molecular weights of 28, 27 and 22 kDa were identified in milk from a-casein deficient mice (Fig. 2d) . Mass-spectrometry analysis confirmed that these proteins are breakdown products of band c-casein (Table 4 ). The lower molecular weight b-casein products are also detected by Western blot analysis of milk samples derived from a-casein deficient mice (Fig. 3b) . Analysis of protein extracts from mammary gland tissue suggests that the breakdown products are the predominant intracellular forms of b and c-casein ( Fig. 4a and  b) but are not secreted as efficiently as the full length protein. The caseins are important for ion transport, mainly calcium and phosphate [35, 36] . Not surprisingly we therefore find that the lower casein protein levels in a-casein deficient mice are accompanied by a significantly lower concentration of calcium and phosphate in milk (reduced by around 90% compared to milk derived from wild-type animals; Fig. 5a ).