Abstract: This invention provides a system for efficiently producing differentiated cells from pluripotent cells, such as human embryonic stem cells. Rather than permitting the cells to form embryoid bodies according to established techniques, differentiation is effected directly in monolayer culture on a suitable solid surface. The cells are either plated directly onto a differentiation-promoting surface, or grown initially on the solid surface in the absence of feeder cells and then exchanged into a medium that assists in the differentiation process. The solid surface and the culture medium can be chosen to direct differentiation down a particular pathway, generating a cell population that is remarkably uniform. The methodology is well adapted to bulk production of committed precursor and terminally differentiated cells for use in drug screening or regenerative medicine.

Abstract: The present invention provides transgenic mice deficient in urocortin. Urocortin null mutant mice are hypersensitive to stress and display heightened anxiety-like behaviors in the elevated plus maze and open field tests. These mice also demonstrate physiological alterations in auditory thresholds and distortion product otoacoustic emissions. These results indicate that urocortin plays a modulatory role in anxiety-related behaviors and in contributing to the establishment of auditory thresholds. Such urocortin deficient mutant mice can provide useful models in the study of anxiety pathology and hearing physiology at the biochemical and molecular levels.

Abstract: The subject invention pertains to a transgenic animal model for tumorigenesis having a genome comprising a ras transgene and which is heterozygous or homozygous for a null p27 gene, and methods of using such animal to screen compounds or evaluate treatments for oncogenic and antitumor activity. The subject invention further concerns a transgenic mouse comprising a ras transgene and which has a genome that is wild-type p27+/+, and wherein the mouse has an FVB/N and C57BL/6X 129 genetic background; and methods of using such transgenic mice to screen compounds or evaluate treatments for oncogenic or antitumor activity. Advantageously, the female animals of the subject invention are fertile and capable of nursing their young. The subject invention also pertains to in vitro systems including isolated cells or tissues of animal models for tumorigenesis, which can be used to screen compounds and treatments for oncogenic and antitumor activity.

Abstract: The present invention concerns a chimeric construct comprising a SMC-specific promoter operably linked to a muscle-specific enhancer. It also provides an expression cassette comprising such a chimeric construct to control expression of a therapeutic gene. Finally, the invention relates to a recombinant vector, a viral particle, an eukaryotic host cell, a composition comprising said expression cassette and their use for specific expression in SMCs and for therapeutic or prophylactic purposes, a method for the treatment of a human or animal organism as well as a transgenic non-human animal comprising integrated into its genome the chimeric construct, the expression cassette or the vector of the present invention.

Abstract: Mice in which enhance wound healing occurs can be used to identify genes and gene products which are involved in enhanced wound healing in mammals, including humans. Methods and compositions for treating wounds, including central and peripheral nerve wounds, are also provided.

Abstract: The present invention relates to a canine pre-proGHRH polypeptide, a canine mature GHRH peptide, an isolated polynucleotide which encodes the canine pre-proGHRH or the canine mature GHRH. The invention also encompasses vectors encoding and expressing the canine pre-proGHRH or the canine GHRH which can be used to treat disease and growth hormone deficiencies by gene therapy in vertebrates, in particular in dogs.

Abstract: The present invention relates to panels of reporter expression cassettes and the generation of transgenic non-human animals, wherein said reporter expression cassettes have selected control elements operable linked to reporter genes. The invention includes methods of use thereof for the identification and characterization of the effects of compounds administered to the live transgenic non-human animals.

Abstract: The invention provides a mutant non-human mammal having a disrupted SCA2 gene, in particular, a mutant mouse having a disrupted SCA2 gene. The invention also provides methods of identifying a therapeutic agent for use in treating obesity or memory impairment by administering a compound to the mutant non-human mammal having a disrupted SCA2 gene and screening said mutant non-human mammal for reduced obesity, thereby identifying a therapeutic agent for use in treating obesity.

Abstract: The present invention relates, in general, to a methodology for the generation or nonsegmented negative-strand RNA viruses (Pringle, 1991) from cloned deoxyribonucleic acid (cDNA). Such rescued viruses are suitable for use as vaccines, or alternatively, as plasmids in somatic gene therapy applications. The invention also relates to cDNA molecules suitable as tools in this methodology and to helper cell lines allowing the direct rescue of such viruses. Measles virus (MV) is used as a model for other representatives of the Mononegavirales, in particular the family Paramyxoviridae.

Abstract: This invention provides a method of converting a stem cell into a ventral neuron which comprises introducing into the stem cell a nucleic acid which expresses homeodomain transcription factor Nkx6.1 protein in the stem cell so as to thereby convert the stem cell into the ventral neuron. Provided are methods of diagnosing a motor neuron degenerative disease in a subject. Also provides is a method of treating neuronal degeneration in a subject which comprises implanting in diseased neural tissue of the subject a neural stem cell which comprises an isolated nucleic acid molecule which is capable of expressing homeodomain Nkx6.1 protein under conditions such that the stem cell is converted into a motor neuron after implantation, thereby treating neuronal degeneration in the subject.

Abstract: Alzheimer's disease, Parkinson's disease and Lewy body disease are the most commonly found neurodegenerative disorders in the elderly. The invention is a transgenic mouse that contains two transgenes, human ?-synuclein and human amyloid precursor protein, which are responsible for the formation of the neuritic plaques, Lewy bodies and neurodegeneration seen in the above mentioned diseases. The transgenic mouse is an accurate model for disease by both functional and pathological assays.

Abstract: Methods for detecting parenchymal plaque deposits in the brain of a living mammal are described that include administering a polyamine modified, labeled polypeptide having specific binding affinity for the extracellular deposit, to the living mammal. Isolated ?-amyloid peptides that are polyamine modified and labeled with a radioisotope or contrast agent also are described.

Abstract: Cells and non-human transgenic animals have been engineered to be deficient in the gene encoding the melcanocortin-3 receptor protein (MC-3R). MC-3R deficient transgenic animals have increased fatmass and reduced lean body mass, showing that the MC-3R protein is involved in the regulation of body fat and muscle mass. These MC-3R deficient transgenic animals can be used to select for and test potential modulators of MC-3R. This data allows for methods of screening for MC-3R modulators which effect body weight and associated methods of treating various disorders associated with inappropriate regulation of body weight. The disclosure also relates to a MC-3R/MC-4R double knockout mouse which can be used to select for and test potential modulators (e.g., agonists or antagonists) of MC-3R and/or MC-4R. It is shown that MC-3R serves a non-redundant role, when compared to MC-4R, in the regulation of energy homeostasis.

Abstract: The present invention provides a animal model useful in identifying a molecule controlling in a lymphocyte-specific manner migration and thus elucidating immune-related diseases and pathogenic conditions such as allergy, autoimmune diseases, GvH and graft rejections at a molecular level, or in developing a novel therapy. A nonhuman animal model such as a DOCK2 knockout mouse, in which the function to control lymphocyte migration has been deleted or suppressed, is generated by deleting DOCK2 gene on the chromosome. In this DOCK2 knockout mouse, the function of activating Rac to mediate actin cyteskeleton, the lymphocyte migration function in response to stimuli with chemokines such as SLC, SDF-1, BLC, the homing function to secondary lymphoid organs such as spleen, lymph nodes and Peyer's patches, and the function of emigrating mature thymic T cells into peripheral blood in response to stimulus with chemokine ELC are impaired, and as a result of this, immune responses are suppressed.

Abstract: This invention provides a method of converting a stem cell into a ventral neuron which comprises introducing into the stem cell a nucleic acid which expresses homeodomain transcription factor Nkx6.1 or Nkx6.2 protein in the stem cell so as to thereby convert the stem cell into the ventral neuron. Provided are methods of diagnosing a motor neuron degenerative disease in a subject. Also provides is a method of treating neuronal degeneration in a subject which comprises implanting in diseased neural tissue of the subject a neural stem cell which is capable of expressing homeodomain Nkx6.1 or Nkx6.2 protein under conditions such that the stem cell is converted into a motor neuron after implantation, thereby treating neuronal degeneration in the subject.

Abstract: The present invention intends to provide a non-human animal model of Guillain-Barré syndrome, which can be obtained by immunizing Fc?RIIB-gene-deficient non-human animal with ganglioside GQ1b, and a screening method of a therapeutic agent for Guillain-Barré syndrome using the non-human animal model. A mouse model of Guillain-Barré syndrome is generated by immunizing Fc?RIIB-gene-deficient mice with gangliosides GM1, GM2, GD1a, and GQ1b together with Freund's adjuvant every three weeks four times in total.

Abstract: A method of modifying the electrophysiological function of an excitable tissue region of an individual is provided. The method includes the step of implanting cells into the excitable tissue region. Each implanted cell is (a) capable of forming gap junctions with at least one cell of the excitable tissue region; and (b) capable of forming a functional ion channel or transporter, wherein the functional ion channel or transporter is capable of modifying the electrophysiological function of the excitable tissue region.

Abstract: It has been discovered that when pluripotent stem cells are cultured in the presence of a hepatocyte differentiation agent, a population of cells is derived that has a remarkably high proportion of cells with phenotypic characteristics of liver cells. In one example, human embryonic stem cells are allowed to form embryoid bodies, and then combined with the differentiation agent n-butyrate, optionally supplemented with maturation factors. In another example, n-butyrate is added to human embryonic stem cells in feeder-free culture. Either way, a remarkably uniform cell population is obtained, which is predominated by cells with morphological features of hepatocytes, expressing surface markers characteristic of hepatocytes, and having enzymatic and biosynthetic activity important for liver function.

Abstract: Methods and compositions are provided for modulating, e.g., increasing or decreasing, the expression of telomerase reverse transcriptase (TERT). In the subject methods, the binding interaction of the GC-Box 5 repressor site with a repressor protein (or protein complex including the same) is modulated to achieve the desired change in TERT expression. The subject methods and compositions find use in a variety of different applications, including the immortalization of cells, the production of reagents for use in life science research, therapeutic applications; therapeutic agent screening applications; and the like.

Abstract: The present invention relates to a method of determining whether a test compound is a proliferation-inducing or proliferation-inhibiting agent of ependymal neural stem cells. The method comprises: (a) contacting an ependymal neural stem cell with the test compound: and (b) determining the proliferation of the ependymal neural stem cell, wherein if the proliferation of the ependymal neural stem cell is increased in the presence of the test compound as compared to the absence of the test compound, the test compound is identified as a proliferation-inducing agent or wherein if the proliferation of the ependymal neural stem cell is decreased in the presence of the test compound as compared to the absence of the test compound, the test compound is identified as a proliferation-inhibiting agent.