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Production of low-lactose milk by ectopic expression of intestinal lactase in the mouse mammary gland

Nature Biotechnology volume 17, pages 160–164 (1999)Cite this article

Abstract

We have investigated, in mice, an in vivo method for producing low–lactose milk, based on the creation of transgenic animals carrying a hybrid gene in which the intestinal lactase–phlorizin hydrolase cDNA was placed under the control of the mammary–specific α–lactalbumin promoter. Transgenic females expressed lactase protein and activity during lactation at the apical side of mammary alveolar cells. Active lactase was also secreted into milk, anchored in the outer membrane of fat globules. Lactase synthesis in the mammary gland caused a significant decrease in milk lactose (50–85%) without obvious changes in fat and protein concentrations. Sucklings nourished with low–lactose milk developed normally. Hence, these data validate the use of transgenic animals expressing lactase in the mammary gland to produce low–lactose milk in vivo, and they demonstrate that the secretion of an intestinal digestive enzyme into milk can selectively modify its composition.

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Figure 1: Ectopic expression of lactase in the mammary gland of transgenic αLc/LPHp mice.
Figure 2: Histologic detection of lactase and α–lactalbumin in the mammary gland of αLc/LPHp–1 mice.
Figure 3: Lactase expression in the milk of αLc/LPHp females.
Figure 4: (A) Milk proteins (70 μg per lane) from αLc/LPHp–1 to αLc/LPHp–4 females at day 10 of lactation (lanes 1–4) and from a control nontransgenic littermate (lane 5) were separated by 12% SDS–PAGE and visualized by Coomasie blue staining.

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Acknowledgements

We are most grateful to M.–G. Stinnakre and to S. Soulier (CIJ, INRA) for their technical help in the generation and identification of the transgenic founder mice.

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale, Unité 381, Strasbourg, France

    Bernard Jost, Jean–Luc Vilotte, Isabelle Duluc, Jean–Luc Rodeau & Jean–Noël Freund

  2. Institut National de la Recherche Agronomique, CIJ,, Jouy–en–Josas, France

    Jean–Luc Vilotte

  3. Centre National de la Recherche Scientifique, UPR 9009, Strasbourg, France

    Jean–Luc Rodeau

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  1. Bernard Jost
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Correspondence to Jean–Noël Freund.

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Jost, B., Vilotte, J., Duluc, I. et al. Production of low-lactose milk by ectopic expression of intestinal lactase in the mouse mammary gland. Nat Biotechnol 17, 160–164 (1999). https://doi.org/10.1038/6158

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