['William', 'Held', '2657', 'Page', '2.', 'Ideally', 'one', 'would', 'have', 'hoped', 'that', 'this', 'latter', 'point', 'were', 'not', 'true.', 'It', 'would', 'be', 'a', 'great', 'experimental', 'advantage', 'if', 'both', 'on', 'and', 'off', 'switching', 'of', 'oncogene', 'expression', 'in', 'the', 'transgenic', 'livers', 'of', 'animals', 'carrying', 'MUP-SV40', 'constructs', 'were', 'possible.', 'Dr.', 'Held', 'has', 'transgenic', 'mice', 'in', 'which', 'MUP', 'BL', '6-11', 'enhancer/', 'promoter', 'sequences', 'are', 'fused', 'with', 'the', 'SV40', 'T-antigen', 'gene.', 'Transgene', 'expression', 'in', 'the', 'livers', 'of', 'these', 'animals', 'is', 'partially', 'regulated', 'by', 'androgen.', 'However', 'in', 'the', 'neoplasms', 'which', 'arise', 'in', 'these', 'livers', 'subsequent', 'to', 'a', 'protracted', 'period', 'of', 'ideopathic', 'dysplastic', 'hyperplasia,', 'transgene', 'expression', 'is', 'found', 'no', 'longer', 'to', 'be', 'androgen~regulated.', 'Most', 'of', 'the', 'transgene', 'work', 'to', 'date,', 'including', 'that', 'part', 'which', 'had', 'been', 'published', 'at', 'the', 'time', 'of', 'application,', 'is', 'based', 'on', 'the', 'MUP', 'BL', '6-11/SV40', 'construct.', 'The', 'MUP', 'BL', '6-11', 'component', 'is', 'not', 'derived', 'from', 'those', 'members', 'of', 'the', '35-member', 'MUP', 'gene', 'complex', 'which', 'exhibit', 'strong', 'male-specific', 'expression', 'in', 'the', 'liver.', 'Promoter/enhancer', 'sequences', 'from', 'other', 'members', 'of', 'the', 'MUP', 'gene', 'class', 'more', 'responsive', 'to', 'androgens', 'must', 'still', 'be', 'isolated,', 'prepared,', 'fused', 'to', 'oncogenes,', 'and', 'successfully', 'incorporated', 'in', 'mouse', 'embryo', 'genomes.', 'Perhaps', 'these', 'constructs', 'will', 'manifest', 'a', 'more', 'radical', 'and', 'complete', 'androgen', 'dependence', 'of', 'retroviral', 'expression', 'in', 'the', 'transgenic', 'setting.', 'Other', 'maneuvers', 'will', 'be', 'undertaken', 'with', 'MUP/oncogene', 'constructs', 'to', 'explore', 'the', 'oncogenic', 'effect', 'of', 'altering', 'the', 'genetic', 'background', 'in', 'which', 'the', 'transgene', 'is', 'inserted.', 'These', 'include', 'experiments', 'in', 'which', 'two', 'of', 'the', 'transgenic', 'lines', 'obtained', 'in', 'the', 'original', 'MUP', 'BL', '6-11', 'will', 'be', 'crossbred', 'with', 'inbred', 'mice', 'of', 'varying', 'natural', 'susceptibility', 'to', 'hepatic', 'carcinogenesis.', 'In', 'one', 'of', 'these', 'transgenic', 'lines,', 'liver', 'carcinomata', 'do', 'not', 'develop', 'in', 'females', 'unless', 'they', 'are', 'treated', 'with', 'androgens', 'whereas', 'neoplasia', 'regularly', 'occurs', 'in', 'the', 'males.']