9513537 Simpson Mammalian sex chromosomes are thought to have evolved from an autosomal pair to a hemizygous state but much of the data which have been generated in the molecular and genetic era do not easily fit into that hypothesis. The Y chromosome contains only a few genes, comparatively speaking. However, one unexpected observation has been that genes which had not recombined since the evolution of the sex chromosomes have been found to be homologous to their X counterparts. One could account for this observation by assuming a similar function for the genes but that would not be acceptable in view of what is known of dosage compensation. The long term goal of this research is to analyze the function of the mammalian sex chromosomes, particularly in the Y-specific region of the Y chromosome. The immediate goal is to create the tools and transgenic mouse strains for the purpose of Y chromosome gene targeting. An embryonic stem cell line with a Y duplication will be created; a genomic library isogenic to the embryonic stem cell line and a strain of transgenic mice needed for targeting experiments will also be created. %%% Our knowledge of how the sex chromosomes function to produce the two sexes without either an overdose or underdose of gene products from those genes found on the sex chromosomes and whether the genes on the two chromosomes are functionally identical is very limited. The production of the necessary tools for asking such questions at the molecular level will make it possible to expand our understanding of the mechanisms used to compensate for the inequality of chromosome number in males and females, particularly in mammals. ***