title: Expression of cDNA-encoded human acid alpha-glucosidase in milk of transgenic mice.
abstract: Enzyme replacement therapy is at present the option of choice for treatment of lysosomal storage diseases. To explore the feasibility of lysosomal enzyme production in milk of transgenic animals, the human acid alpha-glucosidase cDNA was placed under control of the alpha S1-casein promoter and expressed in mice. The milk contained recombinant enzyme at a concentration up to 1.5 micrograms/ml. Enzyme purified from milk of transgenic mice was internalized via the mannose 6-phosphate receptor and corrected enzyme deficiency in fibroblasts from patients. We conclude that transgenically produced human acid alpha-glucosidase meets the criteria for therapeutic application.
authors.affiliation: Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: A G
authors.initials: AG
authors.lastname: Bijvoet
authors.forename: M A
authors.initials: MA
authors.lastname: Kroos
authors.forename: F R
authors.initials: FR
authors.lastname: Pieper
authors.forename: H A
authors.initials: HA
authors.lastname: de Boer
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
authors.forename: A T
authors.initials: AT
authors.lastname: van der Ploeg
authors.forename: M P
authors.initials: MP
authors.lastname: Verbeet
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018076:DNA, Complementary / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology; D005087:Glucan 1,4-alpha-Glucosidase / Q000096:biosynthesis* / Q000235:genetics; D006009:Glycogen Storage Disease Type II / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D008892:Milk / Q000201:enzymology*; D011994:Recombinant Proteins / Q000096:biosynthesis*; D000520:alpha-Glucosidases
chemical_list: D018076:DNA, Complementary; D011994:Recombinant Proteins; D000520:alpha-Glucosidases; D005087:Glucan 1,4-alpha-Glucosidase