The major physiological function of milk is the transport of amino acids, carbohydrates, lipids and minerals to mammalian offspring. Caseins, the major milk proteins, are secreted in the form of a micelle consisting of protein and calcium-phosphate. We have analysed the role of the milk protein alpha-casein by inactivating the corresponding gene in mice. Absence of alpha-casein protein significantly curtails secretion of other milk proteins and calcium-phosphate, suggesting a role for alpha-casein in the establishment of casein micelles. In contrast, secretion of albumin, which is not synthesized in the mammary epithelium, into milk is not reduced. The absence of alpha-casein also significantly inhibits transcription of the other casein genes. alpha-Casein deficiency severely delays pup growth during lactation and results in a life-long body size reduction compared to control animals, but has only transient effects on physical and behavioural development of the pups. The data support a critical role for alpha-casein in casein micelle assembly. The results also confirm lactation as a critical window of metabolic programming and suggest milk protein concentration as a decisive factor in determining adult body weight.
- mammary-gland development
- equilibrium thermodynamic model
- later obesity risk
- protein secretion
- transgenic mice