Abstract: An aim is to produce a suitable foreign protein in egg white in transgenic birds at levels equivalent to or higher than the expression levels achieved using an ovalbumin promoter or an actin promoter, and to reduce the great burden on birds by reducing the expression at sites other than the oviduct while achieving expression sufficient to predict the expression levels before the birds reach sexual maturity. Provided is a transgenic bird containing a nucleic acid base sequence in chromosome in a cell that forms the oviduct, the sequence containing: (a) an avian endoplasmic reticulum chaperone promoter; and (b) a nucleic acid base sequence encoding a suitable foreign protein, functionally linked to the promoter. Also provided is a method for producing a suitable foreign protein, including recovering the suitable foreign protein from the transgenic bird.

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 of generating modified embryos and mammals by introduction of donor cells into an early stage embryo are provided, such that the resulting embryo and animal generated therefrom has a significant contribution to all tissues from the donor cells and is capable of transmitting the donor cell DNA.

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: The present invention provides (1) a method for producing a non-human animal having a humanized liver, comprising transplanting human hepatic stem cells and/or hepatic progenitor cells and/or immature hepatocytes to a liver-damaged non-human animal to induce the differentiation of the cells into hepatocytes, (2) a non-human animal having a humanized liver, produced by the method, (3) a method for examining the pharmacokinetics and/or hepatotoxicity of a test substance, comprising using the animal, (4) a method for producing human hepatocytes, comprising transplanting human hepatic stem cells and/or hepatic progenitor cells and/or immature hepatocytes to a liver-damaged non-human animal to induce the differentiation of the cells into hepatocytes, and (5) a method for examining the pharmacokinetics and/or hepatotoxicity of a test substance, comprising using human hepatocytes produced by the method.

Abstract: The present invention relates to the method and use of reef coral fluorescent proteins in making transgenic red, green and yellow fluorescent zebrafish. Preferably, such fluorescent zebrafish are fertile and used to establish a population of transgenic zebrafish and to provide to the ornamental fish industry for the purpose of marketing. Thus, new varieties of ornamental fish of different fluorescence colors from a novel source are developed.

Abstract: The present invention concerns new modular base-per-base specific nucleic acid binding domains (MBBBD) derived from newly identified proteins from the bacterial endosymbiont Burkholderia Rhizoxinica and their use for engineering nucleic acid processing enzymes, such as specific endonucleases or transcription activators.

Abstract: A pig myostatin gene locus and uses thereof are provided. Also provided includes an expression cassette comprising a promoter, a foreign gene and a following terminator; the promoter is a DNA molecule as set forth in any of 1)-4): 1) nucleotides at positions 2642-3778 starting from the 5? end of SEQ ID NO. 1 in the sequence listing; 2) nucleotides as set forth in SEQ ID NO. 1 in the sequence listing; 3) a DNA molecule, hybridizing and having the same function with the DNA sequence as defined in 1) or 2) under stringent condition. Experiments show that the pig myostatin gene locus provides a valuable gene source for gene targeting, as well as introducing and expressing a foreign gene at this site.

Abstract: Mice are provided that comprise a reduction or deletion of ADAM6 activity from an endogenous ADAM6 locus, or that lack an endogenous locus encoding a mouse ADAM6 protein, wherein the mice comprise a sequence encoding an ADAM6 or ortholog or homolog or fragment thereof that is functional in a male mouse. In one embodiment, the sequence is an ectopic ADAM6 sequence or a sequence that confers upon a male mouse the ability to generate offspring by mating. Mice and cells with genetically modified immunoglobulin heavy chain loci that comprise an ectopic nucleotide sequence encoding a mouse ADAM6 or functional fragment or homolog or ortholog thereof are also provided.

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: Compositions and methods for making livestock with a polled allele are presented, including migrating a polled allele into a bovine species without changing other genes or chromosomal portions.

Abstract: The present invention relates to a recombinant vector and a transgenic mouse for expressing human ferritin in a tissue non-specific manner, and more particularly, to a vector prepared by operably linking a human ferritin gene to a promoter including a cytomegalovirus (CMV) early enhancer element and a ?-actin promoter, and a transgenic mouse expressing human ferritin in a tissue non-specific manner, which is transformed with the vector. Further, the present invention relates to a method for preparing a transgenic mouse, and a method for monitoring cell or tissue therapy using the transgenic mouse.

Abstract: Methods and means are provided for monitoring and modulating reduction of gene expression in eukaryotic organisms, using double stranded RNA comprising, in addition to the dsRNA region comprising nucleotide sequences homologous to the target gene, additional dsRNA regions designed to down regulate a second gene or which are unrelated to the target gene.

Abstract: The present invention provides a new and improved method for producing hybrid silk and like fibers. The invention provides a method of sequence of use which has many advantages over prior art.

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 provides a method of identifying an animal having a genotype associated with resistance to bacterial infection comprising the steps of: (a) providing a sample from said animal; (b) determining the alleles at one or more markers of the SAL1 locus to identify the genotype of the marker, wherein said SAL1 locus lies between 54.0 MB to 54.8 MB of chicken Chromosome 5 or an equivalent thereof; and (c) determining whether the genotype is a genotype associated with resistance to bacterial infection.

Abstract: The present invention relates, e.g., to a method for predicting the embryonic progression of a preimplantation embryo, comprising measuring in the insemination medium (IM) in which an oocyte was fertilized and subsequently incubated in vitro, thereby generating a pre-implantation embryo, at 18-24 hrs post fertilization, the levels of nitric oxide metabolites (NOx) in the insemination medium (IM), wherein a level of NOx of at least about 1.3 ?M indicates that the preimplantation embryo is likely to progress to the blastocyst stage by culture day (CD) 5.

Abstract: WD-repeat proteins are very diverse, yet these are structurally related proteins that participate in a wide range of cellular functions. WDR13, a member of this family, is conserved from fishes to humans and localizes into the nucleus. To understand the in vivo function(s) of Wdr13 gene, we have created and characterized a mutant mouse strain lacking this gene. The mutant mice had higher serum insulin levels and increased pancreatic islet mass as a result of the enhanced beta cell proliferation. While a known cell cycle inhibitor, p21, was down regulated in the mutant islets overexpression of WDR13 in the pancreatic MIN6 cell line resulted in upregulation of p21, accompanied by retardation of cell proliferation. We suggest that WDR13 is a novel negative regulator of the pancreatic beta cell proliferation. Co-immunoprecipitation experiments showed that this protein interacts with estrogen receptors and various HDACs.

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 transgenic fluorescent orange ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.

Abstract: A genetically modified livestock animal comprising a genome that comprises inactivation of a neuroendocrine gene selective for sexual maturation, with the inactivation of the gene preventing the animal from becoming sexually mature. Methods of using, and processes of making, the animals are taught.

Abstract: The present invention provides a rat embryonic stem cell characterized by having the following properties of (a) expressing Oct3/4 gene and Nanog gene, (b) positive for alkaline phosphatase activity, (c) having an embryoid body forming ability, (d) expressing SSEA (Stage-Specific Embryonic Antigen)-1 and SSEA-4, (e) having the same number of chromosomes as does a normal rat cell, (f) capable of being subcultured and holding the undifferentiated state, (g) having in vitro pluripotency, (h) having a potential to differentiate for cells of three embryonic germ lineages, (i) having teratoma formation ability, and (j) having an ability to produce a chimeric rat, a method of establishing the aforementioned rat embryonic stem cell and the like.

Abstract: The disclosure relates to genetically modified swine wherein at least one allele of a SIGLEC1 gene has been inactivated and/or at least one allele of a CD163 gene has been inactivated. Genetically modified swine having both alleles of the SIGLEC1 gene and/or both alleles CD 163 gene inactivated are resistant to porcine reproductive and respiratory syndrome virus (PRRSV). Methods for producing such transgenic swine are also provided.

Abstract: The present invention relates to a method for preparing a transformed Caenorhabditis elegans (C. elegans) which reacts to glucose by exhibiting fluorescence, and to a method for screening for a candidate substance and for a novel gene capable of regulating glucose metabolism and metabolic diseases using the transformed Caenorhabditis elegans. The transformed Caenorhabditis elegans of the present invention is prepared such that changes in glucose may be easily observed on a real-time basis using a fluorescent microscope. The transformed Caenorhabditis elegans of the present invention enables substances for regulating glucose metabolism to be quickly and accurately discovered, and further, may be expected to significantly contribute to studies on a variety of incurable metabolism-related diseases such as obesity, diabetes, and the like.

Abstract: Genetically modified non-human animals are provided that express an immunoglobulin variable domain that comprises at least one histidine, wherein the at least one histidine is encoded by a substitution of a non-histidine codon in the germline of the animal with a hisidine codon, or the insertion of a histidine codon in a germline immunoglobulin nucleic acid sequence. Immunoglobulin genes comprising histidines in one or more CDRs, in an N-terminal region, and or in a loop 4 region are also provided. Immunoglobulin variable domains comprising one or more histidines (e.g., histidine clusters) substituted for non-antigen-binding non-histidine residues. Non-human animals that are progeny of animals comprising modified heavy chain variable loci (V, D, J segments), modified light chain variable loci (V, J segments), and rearranged germline light chain genes (VJ sequences) are also provided. Non-human animals that make immunoglobulin domains that bind antigens in a pH-sensitive manner are provided.

Abstract: Non-human totipotent or pluripotent cells are provided comprising at a genomic locus a self-excisable, recombinase expression cassette flanked with recombination recognition sites, wherein a recombinase gene is operably linked to a promoter that is active in a post-meiotic spermatid stage when cytoplasmic bridging occurs between spermatids. Compositions and methods are provided for making cassette-deleted F1 non-human animals, wherein the methods comprise employing totipotent or pluripotent cells containing a self-excisable, recombinase expression cassette.

Abstract: Mice comprising a human p16 transgene operably linked to an inducible promoter and capable of controlled expression of p16 are provided. Also provided are cells, tissues, and organs obtainable from such mice, and methods for producing p16 transgenic mice.

Abstract: A genetically modified livestock animal comprising a genomic modification to an eIF4G gene. Cells, genes, and proteins encompassing a protease-resistant eIF4G protein or gene.

Abstract: The present invention relates to a transgenic pig as a model for studying a cone affecting disease, in particular a cone dystrophy or cone-rod-dystrophy, wherein the pig model expresses a dominant negative guanylate-cyclase-2D (GUCY2D) protein, in particular a GUCY2D protein comprising at least one mutation responsible for the appearance of a CORD6 cone dystrophy in a human being. The invention further relates to methods by which the transgenic pig is produced, to uses of said transgenic pig or of one of its elements to identify new biomarkers of a cone affecting disease and/or new compounds for preventing or treating such a disease. Novel methods for preventing or treating a cone affecting disease or for evaluating conditions needed to alleviate such a disease are further herein described.

Abstract: The present invention relates to transgenic green ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.

Abstract: The present invention provides a genetically-modified non-human animal whose somatic and germ cells contain an exogenous gene encoding a recombinant fusion protein, wherein the presence, and expression, of said recombinant fusion protein renders said genetically-modified non-human animal sterile. Tools for generating such sterile genetically-modified non-human animal as well as methods of use thereof are also provided.

Abstract: A miRNA expression vector including SEQ ID NO. 11. The vector is capable of improving the fertility of animals by inhibiting the expression of inhibin.

Abstract: The invention relates to a non-human transgenic mammal with an IgH locus modified by replacement of the switching sequence S? with all or part of a transgene comprising the gene C? of a class A human immunoglobulin, including at least the exon, coding for the CH3 domain and the membrane exon and the applications of the above for the production of humanized class IgA antibodies.

Abstract: A genetically modified non-human animal is provided, wherein the non-human animal expresses an antibody repertoire capable of pH dependent binding to antigens upon immunization. A genetically modified non-human animal is provided that expresses human immunoglobulin light chain variable domains derived from a limited repertoire of human immunoglobulin light chain variable gene segments that comprise histidine modifications in their germline sequence. Methods of making non-human animals that express antibodies comprising histidine residues encoded by histidine codons introduced into immunoglobulin light chain nucleotide sequences are provided.

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: 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 transgenic green ornamental fish, as well as methods of making such fish by in vitro fertilization techniques. Also disclosed are methods of establishing a population of such transgenic fish and methods of providing them to the ornamental fish industry for the purpose of marketing.

Abstract: Mice, embryos, cells, and tissues having a restricted immunoglobulin heavy chain locus and an ectopic sequence encoding one or more ADAM6 proteins are provided. In various embodiments, mice are described that have humanized endogenous immunoglobulin heavy chain loci and are capable of expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof that is functional in a male mouse. Mice, embryos, cells, and tissues having an immunoglobulin heavy chain locus characterized by a single human VH gene segment, a plurality of human DH gene segments and a plurality of human JH gene segments and capable expressing an ADAM6 protein or ortholog or homolog or functional fragment thereof are also provided.

Abstract: A LAGLIDADG homing endonuclease variant, having mutations in two separate subdomains, each binding a distinct part of a modified DNA target half-site, said LAGLIDADG homing endonuclease variant being able to cleave a chimeric DNA target sequence comprising the nucleotides bound by each subdomain. Use of said herodimeric meganuclease and derived products for genetic engineering, genome therapy and antiviral therapy.

Abstract: A method, called GETWISE, for targeting mouse genes is described. GETWISE is designed to increase the frequency of homologous recombination, facilitate screening, widen the applicability of engineered animals and circumvent intrinsic gene targeting problems. GETWISE utilizes the principle of modulating gene expression by targeting tetracycline-responsive elements into a specific locus. In GETWISE alleles, control of gene expression is transferred from the endogenous to a tetracycline-inducible promoter. Endogenous promoters now control expression of the reporter gene luciferase. Breeding of GETWISE carriers with tTA/rtTA carriers enables investigators to modulate gene expression in a ubiquitous or tissue-specific manner, depending on the presence of doxycycline. GETWISE enables the study of loss or gain of gene expression in any tissue of choice within a single mouse strain. GETWISE enables the analysis of the gene expression pattern with the luciferase assay.

Abstract: An object of the present invention is to provide a method for introducing a gene into an embryo for production of a human disease model primate animal using a non-human primate animal such as a marmoset. The present invention relates to a method for introducing a foreign gene into an early embryo of a non-human primate animal, which comprises placing early embryos of a non-human primate in a 0.2 M to 0.3 M sucrose solution, so as to increase the volume of the perivitelline spaces, and then injecting a viral vector containing a human foreign gene operably linked to a promoter into the perivitelline spaces of the early embryos.

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: Methods of disrupting germ cell migration and development in a fish embryo by inducing targeted expression of Sdf-1 a or Lif and disruption of the Sdf-1 a gradient or a Lif signaling pathway in the fish embryo have been developed. Plasmid constructs containing a gene encoding Sdf-1 a or Lif and a gene encoding a signaling sequence for targeted expression of Sdf-1 a or Lif have been generated. The plasmids will be administered to a fish or a population of fish to reproductively sterilize the population with efficacy of up to 100%. Transgenic fish of this invention are reproductively incompetent of genetically contaminating a wild fish population.

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 to methods for producing a non human animal model for aortic aneurysm which could provide insight into the diagnosis and treatment of disease. Furthermore, the present invention relates to methods and compositions for the treatment or the prevention of aneurysm in a subject in need thereof.

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 it was applied.

Abstract: Single nucleotide polymorphic sites at positions 3117, 12195, 13244, 13319, and 13516 of the bovine STAT5 gene are associated with improved fertilization rate and/or improved embryo survival rate. Also disclosed are nucleic acid molecules, kits, methods of genotyping and marker assisted bovine breeding methods.

Abstract: An amphidiploid aquatic animal according to the present invention has genomes AB of different species and carries fertile XXXY sex chromosomes. Among a large number of aquatic animals of the first filial generation kept in a closed system, a nonreductive sperm of a male and a nonreductive egg of a female are selected. Then the nonreductive egg is fertilized with the nonreductive sperm to create an amphidiploid aquatic animal having fertile XXXY sex chromosomes. Since this amphidiploid has the XXXY sex chromosomes, it can be crossed with an egg AXBX of an F1 hybrid that produces nonreductive eggs, thus ensuring a stable creation of amphidiploids in the subsequent generations by natural crossbreeding. In the meiotic division, one set of the chromosomes of each species is assuredly distributed to each gamete. Therefore, the trait of the first generation (F1) will be perpetually maintained.

Abstract: Provided are a method for preparing a mammalian ovum or embryo in which zona pellucida has been thinned or eliminated, and a method for fertilization using the mammalian ovum prepared by the aforementioned method. The method for thinning or eliminating zona pellucida of a mammalian ovum or embryo involves treating or culturing the mammalian ovum or embryo (such as an unfertilized ovum, a fertilized ovum, or an embryo in the early stages of development) in a culture medium containing a reducing agent having SH groups (such as reduced glutathione or DTT). The resulting mammalian ovum or embryo (such as an unfertilized ovum, a fertilized ovum, or an embryo in the early stages of development) in which zona pellucida has been thinned or eliminated is capable of realizing an improved fertilization rate and development rate when used for in vitro fertilization, transplantation of a fertilized ovum, or preparation of an embryo in the early stages of development used in the production of a genetically modified animal.

Abstract: The present invention provides methods for attenuating gene expression in a cell, especially in a mammalian cell, using gene-targeted double stranded RNA (dsRNA), such as a hairpin RNA. The dsRNA contains a nucleotide sequence that hybridizes under physiologic conditions of the cell to the nucleotide sequence of at least a portion of the gene to be inhibited (the “target” gene).