Lactation is disrupted by α-lactalbumin deficiency and can be restored by human α-lactalbumin gene replacement in mice

A. Stacey, A. Schnieke, M. Kerr, A. Scott, C. McKee, I. Cottingham, B. Binas, C. Wilde, A. Colman

Research output: Contribution to journalArticlepeer-review

97 Scopus citations

Abstract

Mice carrying either a deletion of the murine α-lactalbumin (α-lac) gene (null allele) or its replacement by the human α-lac gene (humanized allele) have been generated by gene targeting. Homozygous null females are α-lac- deficient, produce reduced amounts of thickened milk containing little or no lactose, and cannot sustain their offspring. This provides definitive evidence that α-lac is required for lactose synthesis and that lactose is important for milk production. Females homozygous for the humanized allele lactate normally, indicating that human α-lac can replace murine α-lac. Mouse and human α-lac expression was compared in mice heterozygous for the humanized allele. The human gene expressed ≃15-fold greater mRNA and ≃-14- fold greater protein than the mouse, indicating that the major determinants of human α-lac expression are close to, or within, the human gene and that the mouse locus does not exert a negative influence on α-lac expression. Variations in α-lac expression levels in nondeficient mice did not affect milk lactose concentration, but the volume of milk increased slightly in mice homozygous for the humanized allele. These variations demonstrated that α- lac expression in mice is gene dosage dependent.

Original languageEnglish
Pages (from-to)2835-2839
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number7
DOIs
StatePublished - 1995
Externally publishedYes

Keywords

  • embryonic stem cells
  • gene targeting
  • lactose
  • milk

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