Abstract: A subpopulation in the CD4.sup.+ 8.sup.+ (DP) thymic blast population is identified that is the precursor for thymic T cells. All such progenitors are c-kit.sup.+. The c-kit.sup.+ subset expresses lower levels of CD4 and CD8 than the large and small DP c-kit- cells. These DP.sup.int c-kit.sup.+ cells differentiate to thymic T cells rapidly on heterogenous thymic stromal cell cultures. Similar maturation takes place in vivo over 4 days. A method for isolating the cells which are c-kit.sup.+ and which express intermediate or low levels of CD4+/CD8+ is also disclosed.

Abstract: Human hematopoietic stem cells are provided by separation of the stem cells from dedicated cells. The stem cells may than be maintained by regeneration in an appropriate growth medium. Means are provided for assaying for the stem cells as to their capability for producing members of each of the hematopoietic lineages.

Abstract: A transgenic, non-human animal model is disclosed which lacks receptors which mediate some of the central nervous system (CNS) actions of serotonin. The animal is preferably from a genus selected from the group consisting of Mus (e.g., mice), Rattus (e.g., rats), Oryctologus (e.g., rabbits) and Mesocricetus (e.g., hamsters). More preferably the animal is a mouse which lacks 5HT.sub.2c receptors. Animals lacking such receptors are overweight due to abnormal control of feeding behavior and are prone to spontaneous death from seizures. Thus, such animals provide an animal model for the testing of drugs which are potentially useful in the treatment of eating disorders and diseases such as epilepsy which result in seizures.

Abstract: Methods are provided for identifying a gene at a random chromosomal locus in the genome of a mammalian cell. The method involves inactivating one copy of the gene by integrating one DNA construct (knockout construct) in that gene copy. The knockout construct includes a positive selection marker region sequence and, in a 5' direction from the selection marker region sequence, a transcription initiation region sequence responsive to a transactivation factor, said transcription initiation region oriented for antisense RNA transcription in the direction away from the selection marker region sequence. The second copy of the gene is inactivated by transforming the cells with a second DNA construct (transactivation construct) containing a gene sequence for the transactivation factor which initiates antisense RNA transcription extending from the knockout construct into the chromosomal locus flanking the knockout construct at its 5' end.

Abstract: Novel regimens are provided for administering foreign genetically modified allogeneic cells to a host by combining the administration of the cells with a reduced regimen of an immunosuppressive agent. Particularly, cells having a reduced level of Class I MHC antigens may be employed in a variety of cellular therapy situations, where foreign cells are engrafted to treat diseased states.

Abstract: Xenogeneic tissue is introduced into an immunocompromised host for interacting with agents and using such interaction for evaluating efficacy of drugs and vaccines, producing xenogeneic monoclonal antibodies, evaluating the effect of the various agents on specific tissues and the like. Particularly, drugs can be evaluated for their efficacy against a wide variety of pathogens which infect xenogeneic tissue, agents can be evaluated for their effect on the xenogeneic immune system and monoclonal antibodies to a predetermined epitope may be produced.

Abstract: T cells are specifically labeled according to their antigen receptor by binding of a multimeric binding complex. The complex is prepared with major histocompatibility complex protein subunits having a homogeneous population of peptides bound in the antigen presentation site. The multimeric MHC-antigen complex forms a stable structure with T cells, thereby allowing for the labeling, identification and separation of specific T cells.

Abstract: Chimeric immunocompromised hosts are provided, comprising human bone marrow of at least 4 weeks from the time of implantation. The bone marrow is found to assume the normal population of bone marrow except for erythrocytes. The bone marrow may be used to study the effect of various agents on the proliferation and differentiation of hematopoietic cells.

Abstract: A human hematopoietic system is provided in an immunocompromised mammalian host, where the hematopoietic system is functional for extended periods of time. Particularly, human fetal liver tissue and human fetal thymus is introduced into an appropriate site of a young immunocompromised mouse at a site supplied with a vascular system, whereby the fetal tissue results in novel formation of functional human bone marrow tissue.

Abstract: Methods and compositions are provided for producing and utilizing nucleic acid and peptide sequences associated with cofactors which bind to transcription factors to enhance transcriptional activity of the transcriptional factors and maintain the transcriptional factors as dimers. The compositions can be used for modulating expression of genes, particularly coordinately regulated genes, as evidenced by the combination of the transcription factors HNF-1.alpha. and -1.beta. with the cofactor DCoH.

Abstract: Functional analysis of genes is provided by employing insertional mutagenesis to a population of DNA molecules containing the gene of interest. The DNA is subjected to a degree of insertion, where the total population of molecules provides for a substantially complete representation of insertion across the length of DNA. The DNA is then subjected to a functional selection. The effect of the selection is determined by amplifying DNA isolated from selected and control populations, and determining whether a particular region is over or underrepresented in the amplified DNA.

Abstract: A method is provided for screening compounds for the ability to supress thymocyte depletion in thymuses of HIV-infected individuals, particularly enhancing the CD4.sup.+ -expressing population as compared to an untreated individual. Particularly, drugs are provided which allow for this result, cyclosporine A being exemplary.