The invention provides a transgene construct, containing a nucleic acid
encoding a photoreceptor specific regulatory sequence, a
membrane-associated polypeptide, and a photoreceptor outer segment
targeting signal. For example, the invention pro-vides a transgene
construct, containing a nucleic acid encoding a rhodopsin promoter, a
membrane-associated polypeptide, and a rod outer segment (ROS) targeting
signal. In addition, the invention provides a gene targeting construct
containing a transgene encoding a polypeptide that contains a rod outer
segment (ROS) targeting signal. The transgene is flanked by 5' and 3' DNA
sequences that are homologous to the rhodopsin gene. Homologous
recombination between the construct and a rhodopsin gene results in
operable association between the transgene and a rod-specific regulatory
sequence. The invention also provides cells and animals whose genome
contain a functional disruption of one or both endogenous rhodopsin gene
alleles, and a transgene encoding a polypeptide that contains a ROS
targeting signal operably associated with a rod-specific regulatory
sequence. The invention constructs, cell and animals can be used to
isolate transgenic polypeptides from the ROS membrane.