Creation and phenotypic analysis of α-lactalbumin-deficient mice

Abstract

α-Lactalbumin is an abundant milk-specific calcium metalloprotein which has an evolutionary relationship to lysozyme. It modifies the substrate specificity of a Golgi galactosyltransferase by forming the lactose synthetase binary complex. Lactose, together with other sugars and diffusible ions, is responsible for the osmotic pressure of milk. To assess the involvement of α-lactalbumin in lactogenesis, α-lactalbumin-deficient mice were created by disrupting the gene by homologous recombination in embryonic stem cells. Homozygous mutant mice are viable and fertile but females cannot feed their offspring. They produce a highly viscous milk that pups appear to be unable to remove from the mammary gland. This milk is rich in fat and protein and is devoid of α-lactalbumin and lactose. The phenotype of heterozygous mice was found to be intermediate, with a 40% decrease in α- lactalbumin but only a 10-20% decrease in the lactose content of their milk compared with wild-type animals. These results emphasize the key function of α-lactalbumin in lactogenesis and open new opportunities to manipulate milk composition.