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Abstract

The present invention relates to an expression system comprising a DNA sequence encoding a polypeptide which ha a biological activity of human .kappa.-casein, the system comprising a 5'-flanking sequence capable of mediating expression of said DNA sequence. In preferred embodiments the 5'-flanking sequence is from a milk protein gene of a mammal such as a casein gene or whey acidic protein (WAP) gene and the DNA sequence contains at least one intron sequence. The invention further relates to DNA sequences, replicable expression vectors and cells harboring said vectors, recombinant polypeptide e.g. in glycosylated form, and milk, infant formula or nutrient supplement comprising recombinant polypeptide. The invention also relates to a method for producing a transgenic non-human mammal comprising injecting an expression system as defined above and optionally a further DNA encoding .beta.-casein or an analog, variant or subsequence thereof into a fertilized egg or a cell of an embryo of a mammal so as to incorporate the expression system into the germline of the mammal and developing the resulting injected fertilized egg or embryo into an adult female mammal. In one embodiment, the endogenous polypeptide expressing capability of the mammal is destroyed and/or replaced with the expression system defined above. The invention further relates to a transgenic non-human mammal such as a mouse, rat, rabbit, goat, sheep, pig, lama, camel or bovine species whose germ cells a somatic cells contain a DNA sequence as defined above as a result of chromosomal incorporation into the non-human mammalian genome, or into the genome of an ancestor of said non-human mammal.

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First Claim