Abstract: The subject invention provides non-human mammalian hosts characterized by inactivated endogenous Ig loci and functional human Ig loci for response to an immunogen to produce human antibodies or analogs thereof. The hosts are produced by multiple genetic modifications of embryonic cells in conjunction with breeding. Different strategies are employed for recombination of the human loci randomly or at analogous host loci. Chimeric and transgenic mammals, particularly mice, are provided, having stably integrated large, xenogeneic DNA segments. The segments are introduced by fusion with yeast spheroplasts comprising yeast artificial chromosomes (YACs) which include the xenogeneic DNA segments and a selective marker such as HPRT, and embryonic stem cells.

Abstract: The present invention provides a recombinant, glucose-regulated insulin producing beta cell whose proliferation is controlled by tetracycline or a derivative thereof. The present invention also provides a method for treating a subject with diabetes using the recombinant beta cell of the present invention.

Abstract: A transgenic mouse having somatic and germ cells in which at least one allele of an endogenous interleukin-1.beta. converting enzyme (ICE) gene is functionally disrupted is provided. The mouse may be heterozygous or, more preferably, homozygous for the ICE gene disruption. In homozygous mice, secretion of mature interleukin-1.beta. and interleukin-1.alpha. is substantially reduced relative to non-mutant mice. The mice of the invention can be used as positive controls to evaluate the efficacy of ICE inhibitors and to identify disease conditions that can be treated with ICE inhibitors. A transgenic mouse having functionally disrupted endogenous ICE genes but which has been reconstituted with a human ICE gene is also provided. This mouse can be used to identify agents that inhibit human ICE in vivo.

Abstract: The present invention is directed to mice which are genetically altered to be deficient in the normal expression of RXR.gamma., to mice heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous or homozygous for such deficiency. The invention further provides mice and cell lines which, in addition to being deficient in RXR.gamma., are genetically altered to be deficient in the expression of RXR.alpha. and/or RXR.beta.. The present invention further provides the use of any of the above mice and cell lines in situations where the absence of RXR.gamma., or the normal expression thereof, is desirable.

Abstract: Disclosed is a mouse in which expression of the gene encoding Osteoprotegerin is suppressed. Also disclosed is a nucleic acid construct useful in preparing such a mouse, and a cell line containing such construct.

Abstract: The present invention provides mouse models of growth hormone insensitivity including Laron syndrome. In particular, the present invention provides transgenic mice incapable of expressing functional growth hormone receptor including mice which further cannot express functional growth hormone binding protein. The invention further provides methods for testing the usefulness of chemical compounds in the treatment of growth hormone insensitivity and diabetic end-organ disease.

Abstract: The present invention provides a vector system that is useful for the generation of mutations in a recombination-based construction method. The invention further includes the incorporation of mutations generated by the method of the present invention into mouse embryonic stem cells and transgenic mice.

Abstract: The present invention discloses MmRad51-deficient transgenic mice and mouse cells, as well as MmRad51/p53-deficient transgenic mice and mouse cells. Also described is a method of screening for proteins that rescue the senescence phenotype in MmRad51/p53-deficient cells.

Abstract: The present invention provides mice which are deficient in the normal expression of one or more members of the RAR or RXR class of receptors, mice which are heterozygous for such deficiency, and to cell lines, preferably pluripotent or totipotent cell lines, which are heterozygous or homozygous for such deficiency. The present invention further provides the use of any of the above mice and cell lines in situations where the absence of at least one RAR or RXR receptor(s), or the normal expression thereof, is desirable.

Abstract: Provided are transgenic mice genetically engineered for a deficiency of the heart-skeletal muscle isoform of the adenine nucleotide translocator protein (Ant1). These mice exhibit histological, biochemical and physiological signs of deficiency in oxidative phosphorylation and energy generation, and these mice provide the first animal model for mitochondrial myopathy and hypertrophic cardiomyopathy. This animal model is used in methods for testing compounds for therapeutic value in treating failure to exchange ATP and ADP across the mitochondrial inner membrane, OXPHOS deficiency and in treating cardiac hypertrophy.

Abstract: A transgenic mouse whose genome comprises a disruption of the endogenous growth differentiation factor-11 (GDF-11) gene is disclosed. Also disclosed are methods for making such mice. The mice exhibit a phenotype of increased muscle tissue.

Abstract: A transgenic mouse with alterations in the H2-Ma gene is prepared by introduction of an altered H2-Ma gene into a host mouse. The resulting transgenic mice do not produce functional H2-M molecules.

Abstract: A transgenic mouse whose genome comprises a disruption of the endogenous growth differentiation factor-8 (GDF-8) gene is disclosed. Also disclosed are methods for making such mice. The transgenic mice exhibit a phenotype of increased muscle tissue.

Abstract: The present invention provides a transgenic mouse containing a transgene, said transgene comprising a truncated Nur77 (.DELTA.Nur77) gene. Also provided is a double transgenic mouse, wherein said double transgenic mouse comprises the .DELTA.Nur77 transgenic mouse backcrossed with the D.sup.b /HY T cell receptor transgenic mouse.

Abstract: The present invention provides a transgenic mouse comprising a disrupted hepsin gene. In particular, the invention provides methods of making the transgenic mouse comprising the disrupted hepsin gene by utilizing a hepsin targeting vector for homologous recombination in mouse embryonic stem cells. Also, nucleotide and amino acid hepsin sequences are disclosed.

Abstract: A transgenic animal with alterations in an thrombin receptor gene is prepared by introduction of an altered thrombin receptor gene into a host animal. The resulting transgenic animals do not produce functional thrombin receptor molecules.

Abstract: Transgenic mice carrying two transgenes, the first coding for a transactivator fusion protein comprising a tet repressor and a polypeptide which directly or indirectly activates in eucaryotic cells, and the second comprising a gene operably linked to a minimal promoter operably linked to at least one tet operator sequence, are disclosed. Isolated DNA molecules (e.g., targeting vectors) for integrating a polynucleotide sequence encoding a transactivator of the invention at a predetermined location within a second target DNA molecule by homologous recombination are also disclosed. Transgenic mice having the DNA molecules of the invention integrated at a predetermined location in a chromosome by homologous recombination are also encompassed by the invention. Methods to regulate the expression of a tet operator linked-gene of interest by administering tetracycline or a tetracycline analogue to a mouse of the invention are also disclosed.

Abstract: The present invention relates to transgenic mice in which the biological function of at least one cell cycle regulatory proteins of the INK4 family is altered.

Abstract: The invention features a method which includes the following steps: (a) introducing a transgene into a zygote of a dwarf goat, (b) transplanting the zygote into a pseudopregnant non-dwarf goat, and (c) allowing the zygote to develop to term. In another aspect the invention features a method which includes the following steps: (a) introducing a transgene into an embryo of a dwarf goat, (b) transplanting the embryo into a pseudopregnant non-dwarf goat, and (c) allowing the embryo to develop to term.