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

Andreas F. Kolb; 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

doi:10.1371/journal.pone.0021775

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

Andreas F. Kolb, 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

9 Citations (Scopus)

Abstract

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.

Original language	English
Article number	e21775
Journal	PLoS ONE
Volume	6
Issue number	7
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0021775
Publication status	Published - 26 Jul 2011

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title = "Milk lacking α-casein leads to permanent reduction in body size in mice",

abstract = "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.",

author = "Kolb, {Andreas F.} and Huber, {Reinhard C.} and Lillico, {Simon G.} and Ailsa Carlisle and Robinson, {Claire J.} and Claire Neil and Linda Petrie and Sorensen, {Dorte B.} and Olsson, {I. Anna S.} and Whitelaw, {C. Bruce A.}",

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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

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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.

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

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