Abstract: A method for detecting a genetic polymorphism associated with Lavender Foal Syndrome or a predisposition thereto in a subject, the method including screening a genomic material sample from the subject for the presence of at least one polymorphism in a MYO5A gene.

Abstract: The present invention relates to a method for integrating a gene fragment inserted between a pair of transposon sequences into a chromosome of a mammalian cell, comprising introducing at least one expression vector which comprises a gene fragment comprising a DNA encoding a protein of interest and also comprises a pair of transposon sequences at both terminals of the gene fragment, into a suspension mammalian cell; and a method for producing the protein of interest comprising suspension-culturing a suspension mammalian cell which produces the protein of interest; and an a suspension mammalian cell which expresses the protein of interest.

Abstract: Isolated polynucleotides comprising a DCX mini-promoters are provided. The mini-promoter may be operably linked to an expressible sequence, e.g. reporter genes, genes encoding a polypeptide of interest, regulatory RNA sequences such as miRNA, siRNA, anti-sense RNA, etc., and the like. In some embodiments a cell comprising a stable integrant of an expression vector is provided, which may be integrated in the genome of the cell. The promoter may also be provided in a vector, for example in combination with an expressible sequence. The polynucleotides find use in a method of expressing a sequence of interest, e.g. for identifying or labeling cells, monitoring or tracking the expression of cells, gene therapy, etc.

Abstract: Disclosed herein are methods and compositions for treating disorders associated with angiogenesis or lymphangiogenesis using ALK-1 antagonists.

Abstract: The present invention provides novel methods for improving the efficiency of artificial activation of unfertilized mammalian oocytes by reducing the intracellular concentration of Zn2+ in the oocyte. The methods of the invention may additionally comprise a preceding step of increasing the intracellular concentration of Ca2+ in the oocyte prior to reduction of the intracellular Zn2+ concentration. The invention further provides unfertilized oocytes activated by the disclosed methods and viable mammalian animals produced from unfertilized oocytes activated by the disclosed methods.

Abstract: Provided herein are mitochondrial-nuclear exchanged cells and animals comprising mitochondrial DNA (mtDNA) from one subject and nuclear DNA (nDNA) from a different subject. Methods for producing a mitochondrial-nuclear exchanged animal and animals made by the methods are provided. Also provided are methods of screening for agents useful for treating a disease or disorder using mitochondrial-nuclear exchanged animals or cells, tissues or organs thereof.

Abstract: The disclosure provides methods and compositions for generating conditional knock-out alleles using donor constructs together with sequence-specific nucleases to generate conditional knock-out alleles. Specifically, the donor construct comprises a 5? homology region, a 5? recombinase recognition site, a donor sequence, a 3? recombinase recognition site, and a 3? homology region. Further disclosed are the donor sequences each comprises a target sequence having at least one neutral mutation. Different sequence-specific nucleases can be used with the donor constructs are further disclosed.

Abstract: The invention relates to polynucleotides, particularly chimeric polynucleotides useful for optimal production of functional immunoglobulins with human idiotypes in rodents. The invention further relates to rodents comprising such polynucleotides.

Abstract: The invention provides systems to control gene expression or activity using target molecules.

Abstract: Methods and compositions are provided for translational profiling and molecular phenotyping of specific tissues, cells and cell subtypes of interest. The methods provided herein facilitate the analysis of gene expression in the selected subset present within a heterogeneous sample.

Abstract: Genetically modified non-human animals comprising a human or humanized interleukin-7 (IL-7) gene. Cells, embryos, and non-human animals comprising a human or humanized IL-7 gene. Rodents that express human or humanized IL-7 protein. Genetically modified mice that comprise a human or humanized IL-7-encoding gene in their germline, wherein the human or humanized IL-7-encoding gene is under control of endogenous mouse IL-7 regulatory sequences.

Abstract: The present invention relates to humanisation of antibodies in vivo. The invention provides non-human vertebrates, cells, populations and methods useful for humanising chimaeric antibodies in vivo. Using the present invention it is possible straightforwardly and rapidly to obtain antigen-specific antibodies that are fully human (ie, comprising human variable and constant regions) and have undergone recombination, junctional diversification, affinity maturation and isotype switching in vivo in a non-human vertebrate system. Furthermore, such antibodies are humanised (eg, totally human)—and selected—totally in vivo, and as such the present invention harnesses in vivo filtering for expressibility, affinity and biophysical characteristics in the context of the desired human variable and constant region pairings. This is avoids problems of down-grading antibody characteristics when humanising the constant region of chimaeric antibodies in vitro.

Abstract: The invention provides cells or populations of cells, including non-human animals or non-human mammals having these cells, where the cells or populations of cells are stably tagged, uniquely identified and genetically barcoded by one or more detectable, e.g., fluorescent, proteins; and methods of making and using them. In alternative embodiments, the invention provides methods for tagging, uniquely identifying or genetically barcoding a cell, a population of cells, or a culture of cells by stably transferring, transfecting, transducing, infecting or implanting one or more nucleic acids encoding readable or detectable, e.g., fluorescent, moieties into the cells. In alternative embodiments, the nucleic acids are stably inserted into the cells such that the readable or detectable, e.g., fluorescent, genetic barcoding becomes a stable, heritable characteristic of the cell.

Abstract: The invention relates to isolation of novel ?-actin and ribosomal protein S21 (rpS21) promoters and uses thereof. In particular, this invention features nucleotide sequences for rodent ?-actin promoters including, hamster, rat, and mouse, and hamster rpS21 promoter.

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: 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: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.

Abstract: Non-human animals, e.g., mammals, e.g., mice or rats, are provided comprising an immunoglobulin heavy chain locus that comprises a rearranged human immunoglobulin heavy chain variable region nucleotide sequence. The rearranged human immunoglobulin heavy chain variable region nucleotide sequence may be operably linked to a heavy or light chain constant region nucleic acid sequence. Also described are genetically modified non-human animals comprising an immunoglobulin light chain locus comprising one or more but less than the wild type number of human immunoglobulin light chain variable region gene segments, which may be operably linked to a light chain constant region nucleic acid sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a heavy chain.

Abstract: Methods and compositions for modulating immune responses are provided herein.

Abstract: The invention provides for delivery, engineering and optimization of systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are delivery systems and tissues or organ which are targeted as sites for delivery. Also provided are vectors and vector systems some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells to ensure enhanced specificity for target recognition and avoidance of toxicity and to edit or modify a target site in a genomic locus of interest to alter or improve the status of a disease or a condition.

Abstract: Disclosed are materials and methods for creating customizable traits in animals. In the demonstration of the principle of the subject invention, a keratin-14 specific promoter is used with red fluorescent protein in the loxp cassette, dominant black (?G23) beta defensin 103 in the pigment cassette, and an SV40 (with intron) polyadenylation sequence. When Cre recombinase (or HTNCre) is applied to the animal's skin in a carrier base (e.g., lipid bilayers), fur is permanently genetically modified to turn black in the shape in which the HTNCre was applied.

Abstract: The present invention is directed generally to eukaryotic cells comprising single-celled organisms that are introduced into the eukaryotic cell through human intervention and which transfer to daughter cells of the eukaryotic cell through at least five cell divisions, and methods of introducing such single-celled organisms into eukaryotic cells. The invention also provides methods of using such eukaryotic cells. The invention further provides single-celled organisms that introduce a phenotype to eukaryotic cells that is maintained in daughter cells. The invention additionally provides eukaryotic cells containing magnetotactic bacteria.

Abstract: The present invention relates to genetically altered hybridomas, myelomas and B cells. The invention also relates to utilizing genetically altered hybridomas, myelomas and B cells in methods of making monoclonal antibodies. The present invention also provides populations of hybridomas and B cells that can be utilized to make a monoclonal antibody of interest.

Abstract: The present invention provides transgenic, large non-human animal models of diseases and conditions, as well as methods of making and using such animal models in the identification and characterization of therapies for the diseases and conditions.

Abstract: A genetically modified livestock animal, and methods of making and using the same, the animal comprising a genetic modification to disrupt a target gene selectively involved in gametogenesis, wherein the disruption of the target gene prevents formation of functional gametes of the animal. Animals that create progeny with donor genetics, and methods of making and using the same. Cells, and methods of making and using the cells, with a genetic modification to disrupt a target gene selectively involved in gametogenesis.

Abstract: A transgenic non-human mammal containing a heterologous lambda light chain gene locus, and/or a heterologous kappa light chain gene locus, and/or a heterologous heavy chain gene locus, each of which can re-arrange so that immunoglobulin heavy and light chain genes are formed and expressed in B-cells following antigen challenge.

Abstract: A transgenic non-human mammal containing a heterologous heavy chain gene locus that is capable of producing soluble heavy chain only antibodies and antigen-binding fragments thereof following immunization.

Abstract: The present invention relates inter alia to improvements in the production of chimaeric antibodies in non-human transgenic vertebrates such as mice and rats bearing one or more chimaeric antibody transgenes. In particular, the invention provides for improved non-human vertebrates and cells in which VpreB has been species-matched with the variable region of the chimaeric antibodies. Also, embodiments also provide for species-matching of the entire surrogate light chain for efficient pairing with chimaeric heavy chains during B-cell development in vivo in a non-human transgenic vertebrate setting.

Abstract: Disclosed herein are methods and compositions for delivery of engineered nucleases and donor molecules into the genome of a cell.

Abstract: Transgenic artiodactyls are described as well as methods of making and using such artiodactyls.

Abstract: The invention relates to the provision of antibody therapeutics and prophylactics that are tailored specifically for human use. The present invention provides libraries, vertebrates and cells, such as transgenic mice or rats or transgenic mouse or rat cells. Furthermore, the invention relates to methods of using the vertebrates to isolate antibodies or nucleotide sequences encoding antibodies. Antibodies, heavy chains, polypeptides, nucleotide sequences, pharmaceutical compositions and uses are also provided by the invention.

Abstract: The invention provides Assay Vertebrates comprising a human antigen or epitope knock-in for testing antibodies comprising human variable regions and generated in a related Antibody-Generating Vertebrate. The invention also provides kits and methods involving these vertebrates and antibodies. The invention provides for superior assay models and assay methods of chimaeric and other test antibodies comprising human variable regions.

Abstract: The present invention relates inter alia to fertile non-human vertebrates such as mice and rats useful for producing antibodies bearing human variable regions, in which endogenous immunoglobulin chain expression has been inactivated.

Abstract: The present invention relates generally to tissue differentiation factor (TDF) analogs. More specifically, the invention relates to structure-based methods and compositions useful in designing, identifying, and producing molecules which act as functional modulators of TDF-like receptors. The invention further relates to methods of detecting, preventing, and treating TDF-associated disorders.

Abstract: The invention provides Assay Vertebrates comprising a human antigen or epitope knock-in for testing antibodies comprising human variable regions and generated in a related Antibody-Generating Vertebrate. The invention also provides kits and methods involving these vertebrates and antibodies. The invention provides for superior assay models and assay methods of chimaeric and other test antibodies comprising human variable regions.

Abstract: The present invention provides a method for screening an agent being useful for the treatment of dry eye and/or corneal and conjunctival lesion of dry eye severity level 3 or more according to the report of the International Dry Eye WorkShop (DEWS Report) (2007) and a pharmaceutical composition comprising the agent. The present invention further provides a method for the treatment of dry eye and/or corneal and conjunctival lesion of dry eye severity level 3 or more according to DEWS Report (2007) using the agent.

Abstract: Described are methods for efficiently down regulating the expression of a gene of interest in a cell by use of a modified rodent parvovirus that contains an expressible target specific nucleic acid, preferably an shRNA expression cassette. Also described are cells or organisms comprising said parvovirus.

Abstract: The invention provides for systems, methods, and compositions for manipulation of sequences and/or activities of target sequences. Provided are vectors and vector systems, some of which encode one or more components of a CRISPR complex, as well as methods for the design and use of such vectors. Also provided are methods of directing CRISPR complex formation in eukaryotic cells and methods for selecting specific cells by introducing precise mutations utilizing the CRISPR/Cas system.

Abstract: The present invention relates to the proline rich transmembrane protein 2 (PRRT2) gene, and the identification of mutations and variations in PRRT2 that give rise to seizure and movement disorders. Accordingly, the present invention provides methods for the diagnosis or prognosis of such disorders by identifying alterations in the PRRT2 gene. Identification of alterations in the PRRT2 gene also enables the identification of subjects with an increased likelihood of having an offspring predisposed to such disorders. The present invention also provides an isolated nucleic acid molecule comprising an alteration in the PRRT2 gene, wherein said alteration produces a seizure and/or movement disorder phenotype. Also provided is an isolated PRRT2 polypeptide that comprises an alteration which produces a seizure and/or movement disorder phenotype.

Abstract: The invention concerns the development of a PIK3CA H1047R knock-in non-human animal breast cancer model, and its use for identification of a spontaneous loss-of-function TP53 mutation involved in spindle cell tumor formation. The invention further concerns the identification of additional somatic mutations and copy number aberrations in the breast tumors using this model, and methods and means for the diagnosis and treatment of breast cancer.

Abstract: The amino acid and nucleic acid sequences of a ?5-desaturase enzyme and a ?8-desaturase enzyme are disclosed. The nucleic acid sequences can be used to design recombinant DNA constructs and vectors. These vectors can then be used to transform various organisms, including for example, plants and yeast. The transformed organisms will then produce polyunsaturated fatty acids. The amino acid sequences are useful for generating enzyme-specific antibodies that are useful for identifying the desaturases.

Abstract: The invention provides genetically modified non-human animals that express a humanized MHC II protein (humanized MHC II ? and ? polypeptides), as well as embryos, cells, and tissues comprising the humanized MHC II protein. Also provided are constructs for and methods of making the genetically modified non-human animals. Methods of using the genetically modified non-human animals to study various aspects of the human immune system are provided.

Abstract: The invention discloses methods for the generation of chimaeric human-non-human antibodies and chimaeric antibody chains, antibodies and antibody chains so produced, and derivatives thereof including fully humanised antibodies; compositions comprising said antibodies, antibody chains and derivatives, as well as cells, non-human mammals and vectors, suitable for use in said methods.

Abstract: The present invention provides novel transgenic nonhuman mammals capable of producing human sequence antibodies, as well as methods of producing and using these antibodies.

Abstract: Non-human animals, e.g., mammals, e.g., mice or rats, are provided comprising an immunoglobulin heavy chain locus that comprises a rearranged human immunoglobulin heavy chain variable region nucleotide sequence. The rearranged human immunoglobulin heavy chain variable region nucleotide sequence may be operably linked to a heavy or light chain constant region nucleic acid sequence. Also described are genetically modified non-human animals comprising an immunoglobulin light chain locus comprising one or more but less than the wild type number of human immunoglobulin light chain variable region gene segments, which may be operably linked to a light chain constant region nucleic acid sequence. Also provided are methods for obtaining nucleic acid sequences that encode immunoglobulin light chain variable domains capable of binding an antigen in the absence of a heavy chain.

Abstract: The invention provides genetically modified non-human animals that express chimeric human/non-human MHC I and MHC II polypeptides and/or human or humanized ?2 microglobulin polypeptide, as well as embryos, cells, and tissues comprising the same. Also provided are constructs for making said genetically modified animals and methods of making the same. Methods of using the genetically modified animals to study various aspects of human immune system are provided.

Abstract: In one aspect, the disclosure relates to compositions comprising alpha-1-antitrypsin (AAT) and the production thereof. In some embodiments, the AAT is recombinantly produced. The disclosure also relates to methods of administering compositions comprising alpha-1-antitrypsin (AAT).

Abstract: Methods of using hypermethylated transposons to create genetically modified animals that express interfering RNAs are described.

Abstract: Genetically modified mammals are described which lack the mannan binding lectin associated serine protease MASP-2, together with methods and constructs for their production. Such mammals are useful as models for disorders of the complement system, and in the identification of treatments for such disorders. Also described are mammals which lack the associated protein MAp19; such mammals may also lack MASP-2.

Abstract: Described are mutant luciferases, nucleic acids that encode them, cells and animals expressing them, methods of use thereof, and kits.