Abstract: The invention provides transgenic animals comprising a disruption in the endogenous GPR101 gene and methods of producing such transgenic animals. The invention further provides methods of identifying compounds that modulate GPR101 receptor proteins.

Abstract: The invention generally relates to polyunsaturated fatty acid (PUFA) polyketide synthase (PKS) systems, to homologues thereof, to isolated nucleic acid molecules and recombinant nucleic acid molecules encoding biologically active domains of such a PUFA PKS system, to genetically modified organisms comprising PUFA PKS systems, to methods of making and using such systems for the production of bioactive molecules of interest, and to novel methods for identifying new bacterial and non-bacterial microorganisms having such a PUFA PKS system.

Abstract: A transgenic animal model for evaluating growth, survival and/or metastasis of xenotransplanted normal or tumor cells or tissue is disclosed, in which a human growth factor, hHGF stimulates growth in vivo of human cells or tissue. A strain of Tg mice on the C3H background that is immunocompromised as a result of a homozygous scid gene has been bred which express a nucleic acid encoding hHGF/SE The ectopically expressed hHGF/SF ligand significantly enhances growth of human tumor cell lines and explanted tumor cells or tissue that express the Met receptor for hHGF. Such animals also have an enlarged normal livers and greater than normal liver regenerative capacity. Any Met-expressing hHGF-dependent human cells, including hepatocytes and various stem cells can survive and grow in such animals.

Abstract: The invention provides compositions and methods for the generation of novel non-human transgenic animals which contain an alteration in a gene of interest. These transgenic animals are capable of generating antibodies, e.g., human monoclonal antibodies, specific for the product of a gene of interest that has been functionally disrupted in the transgenic animal. Furthermore, the methods and compositions of the invention are suitable for use in the treatment, diagnosis, and imaging of disease.

Abstract: The invention provides peptides and the nucleic acid sequences that encode them. The invention further provides therapeutic, diagnostic and research methods for diagnosis, treatment, and prevention of apoptosis associated disorders.

Abstract: The invention relates to cells and transgenic non-human mammals having at least one disrupted heparanase allele. The invention further relates to methods of screening therapeutic drug candidates utilizing the heparanase deficient non-human mammals and cells.

Abstract: Materials and Methods related to gene targeting (e.g., gene targeting with transcription activator-like effector nucleases; “TALENS”) are provided.

Abstract: An animal model has been developed where the animals can survive myocardial infarctions caused by diet-induced coronary atherosclerosis, and live with chronic heart failure. This animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and ApoE and the inducible activity of the Mx1-Cre gene. In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SRBI?/?) and an impaired ApoE expressor (Apoeh/h) to generate a strain referred to as Apoeh/hSRB1?/? mice, which is then crossbred to mice that carry the inducible Mx1-Cre transgene. The Apoeh/hSRB1?/? mouse model is genetically modified, enabling the offspring to rapidly and permanently lower their high blood cholesterol levels caused by dietary challenge.

Abstract: The present invention relates to a novel promoter and its use in driving expression of foreign genes in transgenic animals (especially pigs). Accordingly, the present invention provides a method for producing transgenic animals harboring heterologous genes regulated by the promoter of the present invention.

Abstract: Circular nucleic acid vectors that provide for persistently high levels of protein expression are provided. The circular vectors of the subject invention are to characterized by being devoid of expression-silencing bacterial sequences, where in many embodiments the subject vectors include a unidirectional site-specific recombination product hybrid sequence in addition to an expression cassette. Also provided are methods of using the subject vectors for introduction of a nucleic acid, e.g., an expression cassette, into a target cell, as well as preparations for use in practicing such methods. The subject methods and compositions find use in a variety of different applications, including both research and therapeutic applications. Also provided is a highly efficient and readily scalable method for producing the vectors employed in the subject methods, as well as reagents and kits/systems for practicing the same.

Abstract: The present invention describes methods of generating single VL domain antibodies, including chimeric single chain antibodies that comprise of a variable region of a human immunoglobulin ? or ? light chain and a non-human constant region. The non-human constant region is devoid of a first constant domain CH1, and the variable region is devoid of a heavy chain variable domain.

Abstract: The present invention discloses a mutant blue fluorescent protein (BFP) exhibiting, at an aerobic or anaerobic system, larger fluorescent intensity than a BFPvv D7 of SEQ ID NO:2 derived from a wild type BFP, BfgV of SEQ ID NO:1, obtained from Vibrio vulnificus, wherein a set of mutation positions of the mutant BFP corresponding to SEQ ID NO:2 comprises position 176 or position 178. In a preferred embodiment, the set of mutation positions of the mutant BFP corresponding to SEQ ID NO:2 comprises a S176R mutation or a V178I mutation. Moreover, methods of using the blue fluorescent proteins from Vibrio vulnificus for fluorescence resonance energy transfer (FRET) and a blue fluorescent fish are also provided.

Abstract: Transgenic immunodeficient non-human animals according to embodiments of the present invention are described which include in their genome a nucleic acid encoding xenogeneic Stem Cell Factor operably linked to a promoter. Administration of xenogeneic hematopoetic stem cells to the inventive transgenic animals results in engraftment of the xenogeneic hematopoetic stem cells and xenogeneic leukocytes are produced in the animals, without conditioning such as without conditioning by irradiation and without conditioning by a radiomimetic agent.

Abstract: This invention relates to novel protein transduction domains (PTDs) derived from secretory leukocyte protease inhibitor (SLPI). SLPI-derived PTDs are able to deliver cargo moieties in vivo and in vitro into the cytoplasm and nucleus of a host cell. The invention also relates to a transduction complex comprising one or more SLPI-derived PTDs linked or fused to one or more cargo moieties, which may comprise, for example, proteins, nucleic acids, lipids, carbohydrates, small molecules and other chemical compounds. The invention also relates to the manufacture of SLPI-derived PTDs, complexes comprising them; compositions comprising SLPI-derived PTDs or complexes; and utilization of SLPI-derived PTDs or complexes comprising them for therapeutic, diagnostic and research methods involving delivery of heterologous molecules across cellular membranes, and especially, across nuclear membranes.

Abstract: Methods for identifying animals as having reduced body fat and increased bone density are provided herein. Also provided herein are methods for generating animals having reduced body fat and increased bone density. The methods provided herein are based on the effect of TLR4, MD-2, and CD14 activity on body fat and bone density.

Abstract: The present invention provides a method and components thereof of performing genetic modification under a drug-free environment. The method comprises the steps of generating a trapped mammalian cell library by trapper constructs (including the element of piggyBac terminal inverted repeats (TIRs)), reporter constructs, and helper constructs (including a sequence of an internal ribosomal entry site (IRES)). The present art allows: (1) to target & identify the silenced loci; (2) to separate genes with low-level expression at certain differentiation stages; (3) to evaluate the efficiency of gene targeting in the silent or repressed loci. The present invention avoids the biased gene targeting observed in the prior arts, and eliminates the needs of introducing antibiotic genes into the host genome which may lead to a potential threat of drifting antibiotic resistant genes into environment.

Abstract: The invention discloses a recombinant gene which enhances the ability of fish to tolerate low dissolved oxygen (DO) stress and the use thereof. Carp ?-actin gene promoter is used as a promoter and Vitreoscilla hemoglobin gene is used as a target gene, so as to construct the recombinant Vitreoscilla hemoglobin gene driven by carp ?-actin promoter. The modeling organism zebrafish is used as the research object, and the recombinant gene is microinjected into zygotes of zebrafish. After PCR screening and 156 h low DO stress test, transgenic fish are obtained with a survival rate of 92%, which is significantly different from the survival rate of 65% of the control fish group. The vhb transgenic zebrafish obtain hypoxia tolerance. When the recombinant gene is applied to the economically farmed species, i.e., blunt snout bream (Megalobrama amblycephala) and common carp (Cyprinus carpio L.), it enhances their hypoxia tolerance as well.

Abstract: The molecular mechanism underlying degenerative joint disease, also known as osteoarthritis (OA), is not fully understood. Disruption of mitogen inducible gene 6 (Mig-6) in mice by homologous recombination (KO mice) led to early onset OA as revealed by simultaneous enlargement and deformity of multiple joints, degradation of articular cartilage and the development of bony outgrowths or osteophytes within the joint space. The latter appeared to be derived from proliferation of mesenchymal progenitor cells followed by differentiation into chondrocytes. Because of the striking similarity to human OA, Mig-6 KO mice are a useful animal model for studying the mechanism of this disease and for testing new drugs or therapies for treating OA. These KO mice also developed epithelial hyperplasia, adenoma, and adenocarcinoma in organs such as lung, gallbladder, and bile duct. Mig-6 is therefore a tumor suppressor gene and is a candidate gene for the frequent Ip36 genetic alterations found in lung cancer.

Abstract: The present invention provides methods for studying pathogenesis of mammalian viruses. In particular, the present invention provides a nonhuman animal model system for studying disease mechanisms wherein the nonhuman animal model is infected with an animal virus. In a preferred embodiment the animal model is C. elegans and the animal virus is vesicular stomatitis virus (VSV).

Abstract: A genetically modified non-human mammal or cell characterised in that it does not comprise a nucleic acid sequence which itself encodes any endogenous immunoglobulin heavy chain constant region locus polypeptide.

Abstract: The present invention provides in a first aspect a mouse in which the ? (lambda) light chain locus has been functionally silenced. In one embodiment, the mouse ? light chain locus was functional silenced by deletion of gene segments coding for the ? light chain locus. In a further aspect, a mouse containing functionally silenced ? and ? (kappa) L chain loci was produced. The invention is useful for the production of antibodies, for example heterologous antibodies, including heavy chain only antibodies.

Abstract: An I-CreI variant, wherein at least one of the two I-CreI monomers has at least two substitutions, one in each of the two functional subdomains of the LAGLIDADG core domain situated respectively from positions 26 to 40 and 44 to 77 of I-CreI, said variant being able to cleave a DNA target sequence from the human IL2RG gene. Use of said variant and derived products for the prevention and the treatment of X-linked severe combined immunodeficiency.

Abstract: In general, the invention features genetically modified non-human mammals (e.g., bovines and other ungulates), and methods of making these mammals. In particular, the invention features transgenic ungulates having reduced levels of endogenous IgM heavy chain and/or prion protein.

Abstract: The invention provides compositions and methods useful for deriving or culturing vertebrate ES cells. Certain inventive methods comprise deriving or culturing vertebrate ES cells using medium that comprises a compound that replaces Klf4 or c-Myc in generating iPS cells. The invention provides NOD ES cells and methods of deriving or culturing them.

Abstract: The application describes a transgenic insect comprising a developmental stage-specific lethality system. The developmental stage-specific lethality system comprises a first gene expression cassette comprising a first promoter/enhancer element of a developmental stage-specific gene derived from an insect pest species, preferably from a member of the family Tephritidae, a first component of a transactivating system, a second gene expression cassette comprising a second component of the transactivating system, a second promoter responsive to the activity of the transactivating system, and a lethality inducing system. Also, the application describes a method of controlling reproduction in an insect population of interest, comprising providing a plurality of insects according to the invention and allowing the insects to interbreed with insects of the population of interest.

Abstract: Hypercellular nonhuman organisms have functionally inactivated expression of a cyclin inhibitor gene, especially p27. The growth rate of nonhuman organisms are increased such that a desired size is attained more quickly than as compared to nonvariant organisms. Inhibitors of the p27 cyclin dependent kinase inhibitor protein or sequences encoding the protein modulate vertebrate cell cycle progression and increase the proportion of dividing cells to non-dividing cells in a population of treated cells. As the proportion of dividing cells increases, the cell population, e.g., hematopoietic progenitor (stem) cells, is more efficiently used for gene therapy applications. Transgenic animals and plants, and knockout alleles are provided.

Abstract: Transgenic rodents having NGF beta gene mutants in their genomes express NGF beta mutant proteins. The preparation methods of the transgenic rodents, the methods of utilizing the transgenic animals to prepare NGF beta mutant proteins and the resulting NGF beta mutant proteins are provided. The transgenic rodents are useful in preparing human NGF and in the study of the functions of NGF beta mutants and their receptors in the whole animal level, and also useful for screening and purifying NGF beta mutants which have high activity and high security.

Abstract: The present invention provides methods of altering gene expression of embryos to provide compositions and methods for efficient generation of transgenic animals. In particular, the present invention provides compositions and methods for generating germ-line transgenic animals by direct injection of nucleic acid molecules into animals.

Abstract: The present invention provides a transgenic animal model of Alzheimer's Disease designated TgCRND8 as well as a method for making such model, which allows for the characterization of the etiology of the disease as well as for provide a system for the development and testing of potential treatments.

Abstract: An object of the present invention is to provide a method which constantly enables organ regeneration for the purpose of achieving organ regeneration with higher efficiency. It has been discovered that, in a blastocyst complementation method, a next generation is born when a deficiency in an organ, such as pancreas and kidney, is complemented by injection of ES cells into a generated blastocyst, and further discovered that a transgenic animal having a pancreas or a kidney thus complemented can transmit the phenotype to the next generation as a founder. This discovery has revealed that organ regeneration can be accomplished by using such a founder. Thus, the present invention achieved the above-described object.

Abstract: The present invention relates to the production of a transgenic ungulate which comprises a genetic modification that results in inactivation and loss of expression of its endogenous antibodies, and the expression of xenogenous antibodies, preferably human antibodies. This is effected by inactivation of the IgM heavy chain expression and, optionally, by inactivation of the Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of non-bovine antibodies, preferably human antibodies.

Abstract: A method of producing mutant/targeted non-human mammals, such as mutant mice that does not require production of chimera and permits the introduction of multiple mutations in embryos and, thus, avoids the necessity of breeding to combine all of the desired mutations in a single animal. The method is efficient in producing ES mice.

Abstract: The invention is an animal model which exhibits neuropathological and behavioral features associated with human schizophrenia. The invention also encompasses an in vivo method of preparing an animal model of human schizophrenia. Such a model is useful for screening and identifying therapeutic agents for treating human schizophrenia.

Abstract: Provided are non-human mammals comprising a transgenic nucleic acid sequence capable of causing an alteration of expression of Bri2 or Bri3 in the mammal. Also provided are non-human mammals comprising a Bri2 or Bri3 gene under the control of the native Bri2 or Bri3 promoter. Additionally provided are non-human mammals genetically engineered to lack expression of a Bri2 or Bri3 gene. Further, non-human mammals comprising a transgene encoding a Bri2 or Bri3 protein under the control of the ?CaMKII promoter are provided. Non-human mammals comprising a transgene encoding a furin protein are additionally provided. Embryonic stem cells of any of the above-described non-human mammals are further provided. Methods of screening a compound for treatment of a disease characterized by cerebral amyloidosis are additionally provided. Also provided are methods of making transgenic non-human mammals.

Abstract: This present invention provides novel methods for deriving embryonic stem cells and embryo-derived cells from an embryo without requiring destruction of the embryo. The invention further provides cells and cell lines derived without embryo destruction, and the use of the cells for therapeutic and research purposes. It also relates to novel methods of establishing and storing an autologous stem cell line prior to implantation of an embryo, e.g., in conjunction with reproductive therapies such as IVF.

Abstract: The present invention relates to a method for selecting a domestic animal having desired genotypic properties comprising testing the animal for the presence of a parentally imprinted quantitative trait locus (QTL). The invention further relates to the use of an isolated and/or recombinant nucleic acid comprising a QTL or functional fragment derived therefrom to select a breeding animal or animal destined for slaughter having desired genotypic or potential phenotypic properties. In particular, the properties are related to muscle mass, fat deposition, sow prolificacy, and/or sow longevity.

Abstract: Targeting constructs and methods of using them are provided for differentiation-dependent modification of nucleic acid sequences in cells and in non-human animals. Targeting constructs comprising a promoter operably linked to a recombinase are provided, wherein the promoter drives transcription of the recombinase in an differentiated cell but not an undifferentiated cell. Promoters include Blimp1, Prm1, Gata6, Gata4, Igf2, Lhx2, Lhx5, and Pax3. Targeting constructs with a cassette flanked on both sides by recombinase sites can be removed using a recombinase gene operably linked to a 3?-UTR that comprises a recognition site for an miRNA that is transcribed in undifferentiated cells but not in differentiated cells. The constructs may be included in targeting vectors, and can be used to automatically modify or excise a selection cassette from an ES cell, a non-human embryo, or a non-human animal.

Abstract: Provided herein is a recombinant non-human mammal having an immune system including human immune cells and having a liver including human liver cells, and methods for producing the same. Also provided are methods of screening a compound for activity in treating hepatitis, comprising: administering a test compound to a recombinant non-human mammal as described herein; and then detecting the presence or absence of said activity in said mammal (e.g., by biochemical assay), said presence of said activity in said mammal indicating that said compound has activity in treating hepatitis. Methods of making fusion cells useful for the production of human monoclonal antibodies are also provided.

Abstract: The present invention relates to a transgenic animal suitable for modelling Alzheimer's Disease. The present invention also relates to cells and gametes of the transgenic animal of the invention, along with nucleic acids and vectors suitable for generating the transgenic animal. Methods of generating the transgenic animal are also described, along with screening methods utilizing the transgenic animal.

Abstract: A synthetic hCFTR DNA sequence has been developed that produces remarkably high levels of hCFTR mRNA and protein in dosed murine lungs and human cells in culture compared to the natural hCFTR cDNA. This synthetic DNA addresses problems inherent in some natural cDNAs, such as premature transcriptional truncation sites introduced during cDNA synthesis. Introns are initially present in mRNA until the mRNA is processed. cDNA made from processed mRNA is devoid of introns. Thus DNA sequences (exon junctions) are present in a cDNA molecule which are not present in cells in nature. These exon junctions may affect transcription. Methods for improving expression of CFTR are based on sequence changes in cDNA molecules. The improvement methods may be applied to other cDNA molecules which are refractory to in vivo expression efforts. Compositions embodying the sequence changes increase the production of both transgenic mRNA and protein from cDNA molecules.

Abstract: The present invention is directed to a Trypanosome-resistant, non-human transgenic animal whose somatic and germ cells comprise a nucleic acid which encodes an apolipoprotein L-I polypeptide (apoL-I). The apoL-I protein has the amino acid sequence selected from the group consisting of SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4, and SEQ ID NO: 5. The first nucleic acid transgene is operatively associated with at least one expression regulatory sequence. Methods of producing and raising such transgenic animals as well as transgenic eggs and sperm are also disclosed.

Abstract: This invention provides for proteins which are expressed in the avian oviduct, packaged into eggs laid by the avian and removed from the eggs.

Abstract: The present invention relates to a method for producing a modified foreign chromosome(s) or a fragment(s) thereof, which comprises the steps of: (a) preparing a microcell comprising a foreign chromosome(s) or a fragment(s) thereof, and transferring said foreign chromosome(s) or a fragment(s) into a cell with high homologous recombination efficiency through its fusion with said microcell; (b) in said cell with high homologous recombination efficiency, inserting a targeting vector by homologous recombination into a desired site of said foreign chromosome(s) or a fragment(s) thereof, and/or a desired site of a chromosome(s) derived from said cell with high homologous recombination efficiency, thereby marking said desired site; and (c) in said cell with high homologous recombination efficiency, causing deletion and/or translocation to occur at the marked site of said foreign chromosome(s) or a fragment(s) thereof.

Abstract: The invention relates to a cell containing a gene encoding a conditional transgenic surface marker that is detectable upon expression on the surface of the cell, wherein the gene encoding a conditional transgenic surface marker comprises: (i) a promoter, operably linked to (ii) a first transcription sequence, and (iii) a second transcription sequence encoding the surface marker, whereby the first transcription sequence prevents the transcription of the second transcription sequence, whereby the first transcription sequence is conditionally removable such that the second transcription sequence is transcribable, and whereby the surface marker renders the cell sortable through the detection of the conditional transgenic surface marker. Furthermore, the invention relates to a construct for generating such a cell, and to a method for separating such a cell from a population of cells.

Abstract: The present disclosure provides compositions and methods for increasing bone growth and/or enhancing wound healing, for example, fracture repair. The disclosure provides recombinant nucleic acids useful for promoting bone growth. For example, the disclosure provides recombinant nucleic acids that encode a fibroblast growth factor-2 (FGF-2) analog. The disclosure also provides vectors and cells incorporating these nucleic acids, as well as FGF-2 analogs encode by them. The disclosure also provides a mouse system of bone marrow transplantation and methods for producing as well as methods for using the system. Methods for inducing division and/or inducing differentiation of a hematopoietic stem cell are also provided, as are methods for enhancing bone growth and/or wound repair (for example, fracture repair).

Abstract: The invention relates to the generation of mouse models of drug metabolism in which clusters of genes that are involved in drug metabolism have been knocked out. The development of new drugs and chemicals for therapeutic use or for other purposes is extremely complex. Of particular importance is the understanding of how these chemical agents are handled in the body, whether they have appropriate pharmacokinetics and whether, as a consequence of metabolism, any safety issues arise. Many of the proteins that are involved in the metabolism, disposition and elimination of drugs are members of multigene families that exhibit very marked species differences in gene number, function and regulation. For these reasons, experiments carried out in laboratory animals to establish routes of metabolism or toxicity can be severely compromised and, as a consequence, do not faithfully represent the human situation.

Abstract: The present invention relates to a polynucleotide vector comprising the Simian taste-bud specific gene (STG) promoter operatively linked to a reporter gene. In preferred embodiments, the STG promoter is the murine ortholog of the STG promoter. In other preferred embodiments, the STG promoter is the human ortholog of the STG promoter. In some preferred embodiments, the reporter gene is green fluorescent protein (GFP). Additionally provided are vectors comprising the STG promoter operatively linked to a cre-recombinase gene.

Abstract: A mammalian cell comprising a recombinant, functional L-threonine 3-dehydrogenase (EC 1.1.1.103; TDH) gene, methods of making, and methods of use.

Abstract: A method of preparing adult proliferating cells with stem cell properties includes removing tissue from pronephros or pyloric appendates of an intestine of poikilothermic vertebrates, comminuting removed tissue, cultivating comminuted tissue, and propagating cells persisting in a culture.

Abstract: The invention relates to transgenic avians which produce antibodies in the egg white by introducing a nucleic acid sequence into the genome of an avian embryo wherein the nucleic acid sequence comprises a nucleotide sequence encoding an antibody and to the antibodies and to methods related thereto.