TY - JOUR
T1 - Milk lacking α-casein leads to permanent reduction in body size in mice
AU - Kolb, Andreas F.
AU - Huber, Reinhard C.
AU - Lillico, Simon G.
AU - Carlisle, Ailsa
AU - Robinson, Claire J.
AU - Neil, Claire
AU - Petrie, Linda
AU - Sorensen, Dorte B.
AU - Olsson, I. Anna S.
AU - Whitelaw, C. Bruce A.
PY - 2011/7/26
Y1 - 2011/7/26
N2 - 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 α-casein by inactivating the corresponding gene in mice. Absence of α-casein protein significantly curtails secretion of other milk proteins and calcium-phosphate, suggesting a role for α-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 α-casein also significantly inhibits transcription of the other casein genes. α-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 α-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.
AB - 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 α-casein by inactivating the corresponding gene in mice. Absence of α-casein protein significantly curtails secretion of other milk proteins and calcium-phosphate, suggesting a role for α-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 α-casein also significantly inhibits transcription of the other casein genes. α-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 α-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.
UR - http://www.scopus.com/inward/record.url?scp=79960604193&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0021775
DO - 10.1371/journal.pone.0021775
M3 - Journal article
C2 - 21789179
AN - SCOPUS:79960604193
SN - 1932-6203
VL - 6
JO - PLoS Computational Biology
JF - PLoS Computational Biology
IS - 7
M1 - e21775
ER -