COINTEGRATION OF BETA-LACTOGLOBULIN HUMAN SERUM-ALBUMIN HYBRID GENES WITH THE ENTIRE BETA-LACTOGLOBULIN GENE OR THE MATRIX ATTACHMENT REGION ELEMENT - REPRESSION OF HUMAN SERUM-ALBUMIN AND BETA-LACTOGLOBULIN EXPRESSION IN THE MAMMARY-GLAND AND DUAL REGULATION OF THE TRANSGENES/

The effect of co-integration of the entire beta-lactoglobulin (BLG) ge ne or matrix attachment region (MAR) sequences on the expression of va rious BLG/human serum albumin (HSA) gene constructs was tested in tran sgenic mice. These former sequences were chosen because of their repor ted ability to insulate transgenes from the neighboring host genomic D NA sequences and/or to provide a more permissive transcriptional envir onment. When introduced alone, a cDNA-based BLG/HSA construct was expr essed in 60% of transgenic strains and HSA was secreted at levels up t o 0.3 mg/ml into the milk. Upon cointegration with either the entire B LG gene or MAR element, HSA RNA and protein expression were completely abrogated. While the co-integrated BLG gene suppressed the proportion of expresser strains carrying cDNA as well as genomic BLG/HSA constru cts, the MAR element only exerted its negative effect on the cDNA-base d BLG/HSA construct. In transgenics expressing both HSA and BLG, the t issue specificity and developmental patterns of BLG expression were al tered and resembled the less stringent pattern of the BLG/HSA expressi on. These results demonstrate that rescue of transgene expression thro ugh cointegration with BLG or MAR sequences do not apply universally. (C) 1996 Wiley-Liss, Inc.