Abstract: Disclosed are methods, compositions, and systems for transforming silkworms to produce spider silk and analogs of spider silk. In certain embodiments, the method may include inserting a DNA sequence coding for at least a portion of a spider silk fibroin polypeptide, or an analog of a spider silk fibroin polypeptide, positioned between at least a portion of the 5? and 3? ends of a silkworm fibroin gene to generate a fusion gene construct having a sequence that encodes for a polypeptide comprising both spider silk fibroin and silkworm silk fibroin sequences. In certain embodiments, the fused gene is able to replace a native gene present in the silkworm such that the transformed silkworm expresses a polypeptide comprising a spider silk fibroin polypeptide, or an analog thereof, and expresses significantly less of the native silkworm silk.

Abstract: Described are transgenic animals for conditional and inducible cell targeting, that express a dimerizable conditional-STOP caspase 3 transgene.

Abstract: The present invention relates to a method for obtaining an indication of the saltwater tolerance of a fish, and methods for increasing the saltwater tolerance of a fish. In particular, the invention relates to methods involving biomarkers in the transferrin gene which are correlated with high or low saltwater tolerance.

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: A non-human mammal, especially a mouse exhibiting a characteristic of Rothmund-Thomson syndrome prepared by introducing a mutation into exon 13 of RECQL4 gene; and method of preparation thereof are provided.

Abstract: An animal model of coronary heart disease has been developed where myocardial infarct can be induced by altering the animal's diet. In all embodiments, this animal model is a result of reduced activity of scavenger receptor class BI (SR-BI) and apolipoprotein E (ApoE). In a preferred embodiment, the model is a result of crossbreeding two transgenic mouse lines: a knockout of SR-BI (SR-BI?/?) and an impaired ApoE expressor (hypoE). The impaired ApoE gene results in only 2-5% expression of ApoE and a reduction in cholesterol homeostasis. Resulting animals are predisposed to hypercholesterolemia but can live longer than a year on a normal low fat diet. Serum plasma levels can be significantly elevated by changing the animal's diet to one containing high levels of fat and cholesterol. Within a month on a high fat, high cholesterol diet, animals develop atherosclerosis and myocardial infarction occurs.

Abstract: A rat model of diabetic nephropathy is disclosed. In another embodiment of the invention, a method of evaluating a test compound's effect of diabetic nephropathy is disclosed. In one embodiment, this method comprises the steps of (a) exposing the test compound to the rat of claim 1, wherein the rat would develop progressive proteinuria and glomerulosclerosis leading to diabetic nephropathy in the absence of the test compound, and (b) comparing the rat's development of diabetic nephropathy with a control T2DN mimic rat that has not been exposed to the test compound.

Abstract: Transgenic, non-human animal model of cancer, methods of making such animals and methods of using such animals to screen test compounds are provided.

Abstract: This invention provides a nonhuman transgenic mammal carrying transgene comprising the regulatory genes capable of functioning in the hyperacute rejection-occurring local cells and gene encoding human N-acetylglucosaminyltransferase III (GnT-III), or a nonhuman transgenic mammal carrying transgene comprising the regulatory genes and genes encoding GnT-III and the human complement inhibitor. Because of reduced ?-Gal antigens in the hyperacute rejection-occurring local cells or because of both reduced ?-Gal antigens and expression of the human complement inhibitor, the transgenic mammal of this invention can effectively inhibit the hyperacute rejection caused by discordant xenotransplantation. Consequently, this invention provides the transgenic mammal suitable for organ transplantation.

Abstract: The present invention relates to a biological entity, notably a rat, carrying a regulator construct comprising a specific repressor gene and a responder construct comprising at least one segment corresponding to a short hairpin RNA (shRNA) or corresponding to complementary short interfering RNA (siRNA) strands or corresponding to miRNA, said at least one segment being under control of a promoter which contains an operator sequence corresponding to the repressor. The invention further relates to a method for preparing said biological entity and its use.

Abstract: The present invention relates to a triple transgenic animal model for Alzheimer's disease as well as to methods for generating multi-transgenic animals. The present invention also relates to methods for screening biologically active agents potentially useful for treating and/or ameliorating Alzheimer's disease (AD) or AD-type pathologies, compositions useful for treating AD or AD-type pathologies, and methods of treating AD patients.

Abstract: Described herein are methods for predictable, highly selective expression of a transgene in a human or non-human animal. The methods comprise subtractive transgenics, wherein the expression pattern of one selective promoter is subtracted from the expression pattern of a second selective promoter. Provided are non-human transgenic animals exhibiting a highly selective expression pattern and methods of producing such animals. Further provided are methods of selective expression of a transgene in an animal, including a human, by administration of viral vectors.

Abstract: Transgenic silkworms comprising GFP whose expression is regulated by the sericin gene promoter were produced. Observation of the silk glands of the last instar larvae of the silkworms showed fluorescence only in the middle silk glands. GFP was secreted from middle silkgland cells from around the spinning stage, indicating that GFP moved into the gland lumen. Finally, GFP was spun into cocoon filaments, and cocoons containing large amounts of GFP were produced. Thus, by using the promoter region of the sericin gene, recombinant proteins can be produced in the middle silk glands. Furthermore, the recombinant proteins produced in the middle silk glands were readily secreted into the lumen of the middle silk glands.

Abstract: The invention describes a transgenic non-human animal overexpressing neurotrypsin wherein the animal exhibits symptoms of sarcopenia.

Abstract: The present invention is directed to methods to decrease body weight and/or body fat in an animal, e.g., in the treatment of overweight or obese patients (e.g., humans or companion animals), or as a means to produce leaner meat in food stock animals (e.g., cattle, chickens, pigs), and methods to treat eating disorders (e.g., binge eating disorder and bulimia) in patients in need thereof by administering a PDE9 inhibitor. The invention also features biological tools to further study PDE9 function, i.e., genetically-modified mice and animal cells having a PDE9 gene disruption.

Abstract: Provided by this invention are novel intergeneric bivalve shellfish hybrids, including clams and scallops. Also provided are methods for producing the novel hybrids and their progeny.

Abstract: The invention relates to a method of producing a protein of interest, comprising making a non-human transgenic mammal that produces said protein in its milk, obtaining said milk from the non-human transgenic mammal and purifying said protein of interest from the milk. Transgenic bovine animals were generated, which are able to produce human growth hormone in mammary glands. The method involves cloning of a genetic construct encoding hGH gene and beta casein promoter conveniently in an expression vector. It also includes transfection procedures into fetal bovine somatic cells, generally fibroblasts, and the nuclear transfer into enucleated bovine oocytes, generating thus transgenic embryos.

Abstract: An object of the present invention is to provide a mouse which has the characteristics of early developing visceral fat type obesity and also has concurrent diabetes and hyperlipemia and in which the trait is genetically established and recessively inherited. An ICR-derived mouse strain, Daruma, spontaneously developing obesity, exhibiting autosomal recessive inheritance for the trait of spontaneously developing obesity, and becoming obese only in the homozygous type is provided.

Abstract: The present specification provides, inter alia, methods of using Wnt and FZD proteins, genes, FZD and Wnt-specific antibodies and probes in diagnosis and treatment of cancer and for screening test compounds for an ability to treat cancer. Also disclosed are compounds useful for treating cancer such as liver cancer.

Abstract: The present invention is directed, at least in part, to mice which express exogenous complement receptor type 1 (CR1) on red blood cells. The invention also pertains to genetic constructs encoding heterologous CR1 for expression on red blood cells. Methods of using the transgenic animals of the invention to identify and/or evaluate compositions that can reduce the concentration of an agent, e.g., a biologic agent, in the serum, circulation and/or tissues of a subject are also provided.

Abstract: Disclosed is an in vivo method of incorporating exogenous genetic material into the genome of a vertebrate, which involves administering to a male vertebrate's testis a gene delivery mixture comprising a viral vector, such as a retroviral vector, to deliver a polynucleotide encoding a desired trait or product. Also disclosed is an in vitro method of incorporating exogenous genetic material into the genome of a vertebrate, in which germ cells are obtained from a donor male vertebrate and are genetically modified in vitro, before being transferred to a recipient male vertebrate. After the transfer, the male vertebrate bearing the genetically modified germ cells is bred with a female vertebrate such that a transgenic progeny is produced that carries the polynucleotide in its genome. Also disclosed are non-human transgenic vertebrates produced in accordance with the method, including transgenic progeny.

Abstract: The present invention relates to a mutated gene coding for a mutant LAT protein leading to exaggerated TH2 differentiation. The invention relates to biological structures containing the mutant, particularly non-human LAT gene, mutated animals, plasmids, chromosomal DNAs, embryos comprising the mutated gene, and applications thereof. The invention further relates to screening methods for drugs useful for treatment against asthma and allergy. Otherwise, the invention relates to methods for producing IgE antibodies.

Abstract: The present invention relates to transgenic non-human animals, tissues or cells derived therefrom and methods of producing them. The transgenic non-human animals or tissues or cells derived therefrom provide a system capable of expressing human proteins responsible for drug metabolism in place of the homologous endogenous non-human animal proteins and for the controlled expression of human genes introduced into the animal so that the expression of the human genes is regulated in a manner more closely analogous to that seen in vivo in humans.

Abstract: Disclosed is a transgenic knockout mouse whose genome comprises a homozygous disruption in its endogenous FcRn gene. The homozygous RcRn disruption prevents the expression of a functional FcRn protein, resulting in a transgenic knockout mouse in which exogenously administered IgG1 exhibits a substantially shorter half-life, as compared to the half-life of exogenously administered IgG1 in a wild-type mouse. The transgenic knockout mouse with a homozygous RcRn disruption is also unable to absorb maternal IgG in the prenatal or neonatal stage of development. Also disclosed is a transgenic knockout mouse comprising a homozygous FcRn disruption and a human FcRn transgene. The transgenic addition of human FcRn results in a substantial increase in the half-life of exogenously administered human IgG1. Methods of using the transgenic knockout mouse, and cells derived from them, are also disclosed.

Abstract: The invention provides a transgenic non-human animal expressing a perlecan encoding transgene. Also provided is a double-transgenic non-human animal expressing a perlecan and an amyloid encoding transgene. A method of screening for a compound which alters the rate or extent of amyloid deposition is additionally provided. The method consists of: (a) constructing a perlecan transgenic animal; (b) administering an effective amount of a test compound to said perlecan transgenic animal; and (c) determining whether said test compound alters the extent or rate of amyloid deposition. Finally, the invention provides a method of screening for a compound which alters the rate or extent of amyloid deposition. The method consists of: (a) constructing a perlecan/amyloid double-transgenic animal; (b) administering an effective amount of a test compound to said perlecan/amyloid double-transgenic animal; and (c) determining whether said test compound alters the extent o rate of amyloid deposition.

Abstract: Disclosed is an in vivo method of incorporating exogenous genetic material into the genome of a vertebrate, which involves administering to a male vertebrate's testis a gene delivery mixture comprising a viral vector, such as a retroviral vector, to deliver a polynucleotide encoding a desired trait or product. Also disclosed is an in vitro method of incorporating exogenous genetic material into the genome of a vertebrate, in which germ cells are obtained from a donor male vertebrate and are genetically modified in vitro, before being transferred to a recipient male vertebrate. After the transfer, the male vertebrate bearing the genetically modified germ cells is bred with a female vertebrate such that a transgenic progeny is produced that carries the polynucleotide in its genome. Also disclosed are non-human transgenic vertebrates produced in accordance with the method, including transgenic progeny.

Abstract: A gene targeting method for use in a host organism whereby the host organism is transfected with an ends-out donor construct. Further transfecting the host organism with two transgenes expressing endonuclease and recombinase enzymes. The endonuclease and recombinase enzymes are used so that homologous recombination occurs between the DNA segment of the donor construct and a selected gene of the host organism, thus forming a host with containing the recombinogenic donor. The progeny of the host organism, which include the recombinogenic donor are then selected.

Abstract: The present invention is directed to recombinantly engineered mice that are deficient in the expression of both presenilin-1 and presenilin-2. The mice exhibit characteristics of age-dependent cognitive impairments and neurodegeneration similar to those seen in Alzheimer's disease patients. This presenilin-deficient mouse model can be used to screen compounds capable of slowing, preventing or reversing the progression of cognitive impairments and neurodegeneration. The invention is also directed to the development of treatments for Alzheimer's disease based on augmentation or restoration of presenilin function in the brain. On the basis of the findings described herein, the invention is further directed to the development of assays to detect functional presenilin deficiency in human individuals, preferably through analysis of presenilin substrates, which may provide biomarkers useful in the diagnosis of Alzheimer's disease.

Abstract: The present invention relates to a novel animal model for amyloidopathies, especially Alzheimer' disease overexpressing human BACE and human APP London. This novel animal model exhibits several aspects of amyloidopathy. The present invention also relates to a method for producing the double transgenic animals, to cells and cell lines derived from these animals and to a kit comprising these cells. Moreover, a method for the evaluation of the in vivo effects of beta-secretase activity on A-beta peptide generation, amyloidosis, neurodegeneration and AD pathology in these animals is provided.

Abstract: Methods for generating and using novel overexpression activity alleles of a gene in any organism, especially Drosophilia, are provided. Such alleles may be utilized in screening assays, and used to generate dominant-negative forms of bacterial toxins.

Abstract: An animal selected for lacking heparan sulfate 3-O-sulfotransferase-1 activity is provided. This animal exhibits characteristics associated with myxomatous valvular disease and is useful for identifying agents which prevent, delay or treat myxomatous valvular disease. Methods of diagnosing myxomatous valvular disease are also provided.

Abstract: The present invention provides an immunodeficient mouse (NOG mouse) suitable for engraftment, differentiation and proliferation of heterologous cells, and a method of producing such a mouse. This mouse is obtained by backcrossing a C.B-17-scid mouse with an NOD/Shi mouse, and further backcrossing an interleukin 2-receptor ?-chain gene-knockout mouse with the thus backcrossed mouse. It is usable for producing a human antibody and establishing a stem cell assay system, a tumor model and a virus-infection model.

Abstract: A milk or other dairy product, capable of minimizing the onset of disease such as coronary heart disease or enhancing the immune response is derived from animals which are substantially free of the ?-casein A1 allele. Bulk milk can be produced by testing for and culling cows who test positive for the ?-casein A1 allele, or by producing immunoglobulins and other immune response proteins, in cow's milk from animals not possessing the ?-casein A1 allele, or other commercial milk producing animals, to this allele, to counteract the immnunosuppressant substances present that are produced from it, in commercial milking cows such as Holsteins, together with its blending with non-treated milk or the recovery of such immunoproteins.

Abstract: The present invention discloses a method for expressing multiple recombinant proteins in transgenic non-human mammalian milk, characterized in which human clotting factor IX gene and porcine lactoferrin gene are transferred into the mammal by gene injection and embryonic implantation to obtain expression in the milk of transgenic mammal and its filial generation. The method of this invention can maintain the stable expression of multiple recombinant proteins in the transgenic mammal during lactation and stable expression amount proximate to that of the first generation in the offsprings of the transgenic non-human mammal.

Abstract: The invention provides gene-targeted non-human animals comprising a genetically modified apoE gene encodes a recombinant apoE polypeptide displaying domain interaction. The invention further provides cells isolated from the gene-targeted animals, which cells produce a recombinant apoE polypeptide displaying domain interaction. The invention further provides methods of identifying agents that reduce apoE4 domain interaction, and which are useful to treat apoE4-related neurological and cardiovascular disorders.

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: The present application provides a vector for trapping an unknown gene of Drosophila melanogaster, which is a recombinant plasmid comprising the following nucleotide sequences in this order: an artificial consensus splicing acceptor site; a synthetic “stop/start” sequence; a reporter gene; a drug resistance gene; a gene responsible for a detectable phenotype of the Drosophila melanogaster; and a synthetic splicing donor site. The present application also provide a method for trapping an unknown gene of Drosophila melanogaster by using the vector.

Abstract: In humans, approximately 60% of expressed immunoglobulin light chains are of the Kappa type and 40% of the Lambda type. In mice, there is almost no expression from the Lambda locus and over 95% of light chains are of Kappa type. The present invention discloses, among other things, transgenic mice carrying most of the human Ig Lambda light chain locus in their genome. The resulting mice express light chains with Kappa/Lambda ratio similar to the human ratio. Breeding of HuIg Lamda mice to Kappa-deficient mice also is described, as well as the generation of human monoclonal antibodies from transgenic mice with human Ig Lambda locus.

Abstract: The present invention relates to mammals into which foreign DNA has been introduced or in which various modifications or substitutions have been made to an integrin ? subunit, thereby generating transgenic or genetically-engineered non-human mammals. In particular, the present invention provides a transgenic mammal in which the endogenous GP IIIa gene has been replaced with an altered or mutant GP IIIa gene in which one or all of the phosphorylable cytoplasmic tyrosine residues have been replaced with non-tyrosine residues such as phenylalanine. Since the platelets in the blood of the resultant transgenic mammals expressing in wild-type mammals, these genetically-engineered animals provide a critical tool for assessing the importance of the phosphorylation reaction for platelet function. The invention is also useful for studying the effect of the mutant GP IIIa integrin subunit on biological processes other than platelet formation.

Abstract: The present invention provides non-invasive methods and compositions to differentiate, with a high level of sensitivity and specificity, swine that are genetically susceptible to diseases associated with F18 E. coli infection, from resistant swine. DNA polymorphisms in the swine alpha (1,2) fucosyltransferase 1 (FUT1) gene were used to differentiate resistant from susceptible swine. The invention includes a polypeptide with amino acid substitutions, encoded by the nucleotide polymorphisms, a molecular diagnostic assay, and a kit for the differentiation, of E. coli F18-adhesion resistant, heterozygous (carrier) and homozygous susceptible pigs. The molecular test identifies susceptibility to oedema disease and postweaning diarrhea with high sensitivity and specificity, therefore, is useful to swine breeder in their effort to enhance for resistance. Information on the polymorphisms of the present invention provides insight into causation and treatment of E. coli associated intestinal disorders.

Abstract: Methods for breeding mutagenized mice permit detection of genetic loci that in heterozygous mutated form can modify a known index phenotype involves crossing a mutagenized founder strain and a second strain of mice carrying an allele at a locus that confers the index phenotype. In the test generation, clusters of individuals are observed to deviate from the typical phenotype. The genetic material and molecules encoded thereby can be obtained using available methods. Improved and compact methods are also disclosed.

Abstract: The present invention provides fish system as a powerful forward genetic tool to directly identify a number of novel genes involved in cell proliferation in vertebrates without the time consuming and costly maintenance of animals. The invention provides a tool to identify functional characteristics of a protein without prior knowledge of the gene sequence. After identification of the mutant gene in the fish system, the nucleic acid sequence of the gene can be used for identifying a homologue of the gene in another species, for example, in humans.

Abstract: An object of the present invention is to provide a null mutant non-human animal showing salt intake behavior similar to that of wild-type animals under water-sufficient conditions and showing much more intakes of hypertonic saline compared with wild-type animals under water- and salt-depleted conditions, for example, an Nav2 gene-deficient non-human animal, which is useful as a model animal of excessive salt intake experiments. The object will be attained by following process: mouse genomic libraries are screened with rat NaG cDNA as a probe, then Nav2 gene of genomic DNA is isolated, and a targeting vector is constructed by inserting marker gene such as neo gene into the exon of Nav2. After thus constructed targeting vector is induced to ES cells, homologously recombined ES cells are selected, then germ line chimeric mice are constructed with this ES cells strain, and they are hybridized with the wild-type mice and heterozygous mutant mice are obtained.

Abstract: Described herein is a novel gene and its product, WIP, which associates with WASP. The subject invention relates to the isolated WIP gene or cDNA and transgenic mammals that have the WIP gene disrupted in their genome. Also the subject of this invention are methods of treating conditions or diseases in which WIP and/or WASP DNA or protein is deficient and/or defective, for example, mutated or altered, such that an individual is adversely affected. Also described are methods of altering or regulating WIP and its functions in a mammal or in a cell of a mammal, for example in a lymphocyte. A further subject of this invention is an assay to identify drugs which alter the activity of WIP or expression of WIP DNA.

Abstract: A method is provided for measuring in vivo in a transgenic non-human multicellular organism the activity of a cellular enzyme, which organism is transgenic by virtue of comprising one or more nucleic acid constructs encoding a binding domain and a binding partner thereof wherein: (i) the binding domain and/or binding partner comprise a site subject to post-translational modification by the cellular enzyme; (ii) modification of the site by the enzyme affects the interaction between the binding domain and the binding partner; and (iii) the binding domain and the binding partner each comprise a detectable label such that when the binding domain and binding partner interact, a detectable physical characteristic of one or both of the labels is altered, which method comprises measuring the interaction between the binding domain and the binding partner by measuring changes in the physical characteristic in one or more cells of the transgenic organism. A transgenic non-human multicellular organism is also provided.

Abstract: The present invention relates to methods of producing an allelic series of modifications in genes of interest in a cell. In particular, the invention provides methods for using nucleic acid sequence-modifying agents (e.g., chemicals, electromagnetic radiation, etc.) to introduce modifications in any nucleic acid sequence in the genome of a cell. Also provided are sets of cells which contain at least one modification in any gene of interest. The methods and compositions of the invention are useful in determining the function of the gene of interest.

Abstract: A mammal is provided, in which the LKB1 gene can be deleted phase-specifically and tissue-specifically. These mammals are highly useful as tools to reveal the onset mechanism for diseases caused by LKB1 gene deficiency, such as Peutz-Jeghers syndrome and cancers, as well as to develop therapeutic agents, methods, and so on for the diseases.

Abstract: Mammalian somatic cells having a homozygous disruption in the gene which encodes the endonbonuclease RNase L and a homyzgous disruption in the gene which encodes the double-stranded RNA dependent kinase PKR are provided. Methods for producing enhanced levels of recombinant proteins in mammalian cell systems are also provided. In one aspect the method employs cells having a homozygous disruption in the RNase L gene and a homozygous disruption in the PKR gene and comprises transfecting the cells with a nucleic acid, or polynucleotide, encoding a desired, exogenous protein; expressing the exogenous protein in the cell; and isolating the exogenous protein from the transfected cells. In another aspect the method employs RNase L null cells transfected with a nucleic acid encoding a desired, exogenous protein. In another aspect the methods employ mutant cells hating a homozygous disruption in the PKR gene, i.e. PKR null cells.

Abstract: The present invention relates to transgenic animals, as well as compositions and methods relating to the characterization of gene function. Specifically, the present invention provides transgenic mice comprising mutations in an intestinal alkaline phosphatase gene. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and gene function, and as potential treatments for various disease states and disease conditions.

Abstract: This work constitutes a novel approach and methodology, e.g., the in vitro secretion method to isolate the androgenic polypeptide hormone (AH) from the androgenic gland of shrimp or prawns. Alternatively, the AH can be obtained recombinantly by cloning and expressing the AH gene. The AH polypeptide is used to produce phenotypic males, neomales, from genotypic female shrimp or prawns. The neomales find use in the production of sex-skewed and monosex offspring when mated with wild-type female shrimp or prawns. From the sequence of the purified AH polypeptide, oligonucleotide probes are synthesized to clone the AH encoding nucleic acid which is used for recombinant AH polypeptide expression.