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.

Milk Protein Synthesis in the Lactating Mammary Gland: Insights from Transcriptomics Analyses

“…General references [67,68]. Specific references for milk composition are: bovine [4,67,69], mouse and rat [70][71][72][73][74], human [75], pig [55], sheep and goat [76], and Kangaroo [77][78][79] The application of functional genomics and bioinformatics allows for a thorough exploration of the biological complexity of organisms' tissues [34]. Together, these approaches form part of the systems biology framework, i.e., a way to systematically study the complex interactions in biological systems using a method of integration instead of reduction.…”

Behaviour of postnatally growth-impaired mice during malnutrition and after partial weight recovery

“…29 The present study is a first contribution towards the characterization of this potential animal model for early protein malnutrition in terms of general activity, anxiety, short-term, and working memory and pain perception. The model may prove to be useful in studying the effect of severe early postnatal PEM, as the introduction of confounding factors such as differences in maternal care and social environment can be avoided.…”

“…30 Materials and methods Animals, housing, and maintenance Generation of α-casein-deficient dams, milk composition, and the genetic background of the animals have been described previously. 29 In these animals, the lack of α-casein production was accompanied by an overall decrease in casein proteins. Transgenic mice were generated at Genoway (Lyon, France) as a SV129 × C57/BL6 mixed background.…”

“…29 Before weaning and at 8 weeks of age the animals had been individually screened regarding weight development, general health and appearance, and physical development following a phenotyping protocol described previously. 29 After weaning at 23 days of age, the animals were housed in same-sex groups consisting of littermates.…”

Epithelial Xbp1 Is Required for Cellular Proliferation and Differentiation during Mammary Gland Development

“…7A). Furthermore, casein, which is a major component of mouse milk, has a significant effect on maturation of milk secretion and growth of the offspring (30). Therefore, we assessed the expression of genes for mouse milk constitutive proteins in whole mammary lactating gland tissue by qPCR.…”