Milk lacking α-casein leads to permanent reduction in body size in mice

Andreas F Kolb* (Corresponding Author), Reinhard C Huber, Simon G Lillico, Ailsa Carlisle, Claire J Robinson, Claire Neil, Linda Petrie, Dorte B Sorensen, I Anna S Olsson, C Bruce A Whitelaw

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)
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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.

Original languageEnglish
Article numbere21775
Number of pages20
JournalPloS ONE
Issue number7
Publication statusPublished - 18 Jul 2011


  • mammary-gland development
  • equilibrium thermodynamic model
  • later obesity risk
  • endoplasmic-reticulum
  • calcium-phosphate
  • epithelial-cells
  • kappa-casein
  • beta-casein
  • protein secretion
  • transgenic mice


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