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.
authors.affiliation: Molecular Recognition Group, Hannah Research Institute, Ayr, United Kingdom. a.kolb@abdn.ac.uk
authors.forename: Andreas F
authors.initials: AF
authors.lastname: Kolb
authors.forename: Reinhard C
authors.initials: RC
authors.lastname: Huber
authors.forename: Simon G
authors.initials: SG
authors.lastname: Lillico
authors.forename: Ailsa
authors.initials: A
authors.lastname: Carlisle
authors.forename: Claire J
authors.initials: CJ
authors.lastname: Robinson
authors.forename: Claire
authors.initials: C
authors.lastname: Neil
authors.forename: Linda
authors.initials: L
authors.lastname: Petrie
authors.forename: Dorte B
authors.initials: DB
authors.lastname: Sorensen
authors.forename: I Anna S
authors.initials: IA
authors.lastname: Olsson
authors.forename: C Bruce A
authors.initials: CB
authors.lastname: Whitelaw
mesh_terms: D000818:Animals; D017209:Apoptosis; D001522:Behavior, Animal; D015415:Biomarkers / Q000378:metabolism; D049628:Body Size; D001835:Body Weight; D002118:Calcium / Q000378:metabolism; D002364:Caseins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D006262:Health; D007150:Immunohistochemistry; D008321:Mammary Glands, Animal / Q000166:cytology / Q000378:metabolism; D013058:Mass Spectrometry; D051379:Mice; D008892:Milk / Q000378:metabolism*; D008954:Models, Biological; D010710:Phosphates / Q000378:metabolism
chemical_list: D015415:Biomarkers; D002364:Caseins; D010710:Phosphates; D002118:Calcium