HUMAN PARATHYROID-HORMONE AS A SECRETORY PEPTIDE IN MILK OF TRANSGENIC MICE

In a transgenic mouse model we have targeted the expression of recombi nant human parathyroid hormone (hPTH) to the mammary gland yielding hP TH as a secretory, soluble peptide in milk. A 2.5 kb upstream regulato ry sequence of the murine whey acidic protein (WAP) directed the expre ssion of the hPTH cDNA in a fusion gene construct (WAPPTHSV2) containi ng the SV40 small t-antigen intron and polyadenylation site in the 3' end. Established lines of transgenic mice secreted hPTH to milk in con centrations up to 415 ng/ml. Recombinant hPTH recovered from the milk was purified by HPLC and shown to be identical to hPTH standard as ana lyzed by SDS-PAGE followed by immunoblotting. Expression of the WAPPTH SV2 was limited to the mammary gland as analyzed by polymerase chain r eaction (PCR) and Southern blot of reversed transcribed mRNA from diff erent tissues. hPTH is an important bone anabolic hormone and may be a potentially important pharmaceutical for treatment of demineralizatio n disorders such as osteoporosis. We present the transgenic animal as a possible production system for hPTH. (C) 1995 Wiley-Liss, Inc.