Locus-Control-Region-Coupled Beta (S)(Antilles)- and Alpha(2)-Hemoglobin Genes Select for High Alpha(2)-Hemoglobin...

Two transgenic lines of mice were produced which contained the beta(S)(Antilles)- and alpha(2)-hemoglobin genes tandemly coupled to the 'micro' locus control region (&mgr;LCR). The &mgr;LCRbeta(S)(Antilles)alpha(2)-hemoglobin transgenic mice expressed high levels of alpha(2)-hemoglobin while beta(S)(Antilles)-hemoglobin expression was virtually undetectable. Abundant alpha(2)-hemoglobin protein was observed in the blood of transgenic mice, while beta(S)(Antilles)-hemoglobin chains could not be detected. Transgenic red blood cells had substantially decreased sensitivity to osmotic lysis. Attempts to produce homozygotes containing the transgene were unsuccessful. The phenotype of these mice closely resembles that of beta-thalassemic mice. The &mgr;LCRbeta(S)(Antilles)alpha(2) transgenic mice demonstrate that if the &mgr;LCR is coupled to the beta(S)(Antilles)- and alpha(2)-hemoglobin genes in tandem, only the distal alpha(2)-hemoglobin gene is selected for expression to significant levels in adult mice. These results support a reciprocally competitive model for LCR-hemoglobin developmental switching. Copyright 1994 S. Karger AG, Basel