ABSTRACT The invention provides a novel approach to increase immunoglobulinexpression in non-human transgenic animals. For instance, the inventionprovides a method to increase humanized immunoglobulin production in animalsgenetically engineered to express one or several human or humanizedimmunoglobulin transloci. This can be done by overexpressing the apoptosisinhibitor, i.e. a rabbit bcl-2, whose expression is driven by a B-cellspecific promoter specifically in the B-cell of the animal, thereby enhancingthe survival of B-cells. This invention further relates to a method for'selectively enhancing the survival of exogenous B-cells, that is B-cellsexpressing any immunoglobulin transgene locus, over the survival of endogenousB-cells that do not express the transgene locus. Selectivity is achieved byexpressing the apoptosis-inhibitor only within exogenous B-cells, that is, bycoupling exogenous immunoglobulin expression with apoptosis inhibitorexpression. This latter method allows for increased expression and productionof the transgene encoded product(s) over the endogenously producedimmunoglobulin of the transgenic animal. The invention also provides a novelapoptosis-inhibitor, rabbit bcl-2.
展开▼
