Abstract: A transgenic, non-human mammalian animal is capable of expressing a heterologous gene for human or other recombinant physiologically functional fibrinogen holoprotein or individual subunit chain polypeptides thereof or a modified or fusion fibrinogen in mammary glands of the animals and secreting the expressed product into a body fluid. Methodology employing such a mammal yields recombinant physiologically functional fibrinogens, subunit chain polypeptides thereof, and modified or fusion fibrinogens.

Abstract: The invention provides inducible expression systems for making short RNA transcripts that can be used in cells and transgenic animals for a variety of applications, including but not limited to, producing and studying the effects of RNAi and microRNA mediated gene silencing.

Abstract: The present invention relates to compositions and methods for inducing mammary epithelial cell differentiation in mammalian subjects. More specifically, the present invention relates to methods for inducing mammary epithelial cell differentiation which comprise increasing the levels of galanin in the mammary tissue of the subject. In one aspect the present invention relates to a method of increasing milk production in a lactating mammal which comprises increasing the level of galanin or an analog thereof in the mammal. In another aspect the present invention relates to a method of enhancing mammary development in a mammal, the method comprising administering to the mammal galanin or an analog thereof in conjunction with prolactin or an analog thereof. In yet another aspect the present invention relates to a method for inhibiting mammary epithelial tumours by administering an inhibitorially effective therapeutic amount of galanin or an analog thereof.

Abstract: The invention describes a concrete schema which allow domesticated ruminant with disease due to Mycobacterium avium subspecies paratuberculosis to serve as an animal model system in order to assess potential systemic and mucosal effects achieved by attempted therapeutic interventions. A key component of this schema is the recognition of the significance of a positive precipitantion band on agar gel immunodiffusion test in terms of the underlying histopathology and subsequent ability to use such data in evaluation necropsy derived data. A second component is the sequential use of newly developed nesting PCR technology and their abilities to identify (and where indicated quantitate) Map DNA present in feces, blood and milk.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: A method of reconstituting an animal embryo involves transferring the nucleus from a quiescent donor cell into a suitable recipient cell. The donor cell is quiescent, in that it is caused to exit from the growth and division cycle at G1 and to arrest in the G0 state. Nuclear transfer may take place by cell fusion. The reconstituted embryo may then give rise to one or more animals. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: The invention provides modified recombinant nucleic acid sequences (preferably DNA) and methods for increasing the mRNA levels and protein expression of malarial surface protein MSP-1 which is known to be difficult to express in cell culture systems, mammalian cell culture systems, or in transgenic animals. The preferred protein candidates for expression using the recombinant techniques of the invention are MSP-1 proteins expressed from DNA coding sequences comprising reduced overall AT content or AT rich regions and/or mRNA instability motifs and/or rare codons relative to the native MSP-1 gene.

Abstract: The present invention inter alia relates to methods for the prevention, amelioration or treatment of medical conditions associated with an alteration in normal goblet cell function. It also relates to methods of screening for disease-relevant markers indicative of an increased risk of a subject of developing such a condition. It furthermore relates to an animal model useful for studying said conditions and the molecular mechanisms underlying them, and uses of that animal model, for example for the identification of diagnostic markers or agents useful for the prevention, amelioration, or treatment of a goblet cell-related disorder. Novel agents useful in the above methods, and novel pharmaceutical compositions are likewise provided. The invention further relates to screening methods for agonists and antagonists useful for performing said methods.

Abstract: In one aspect, the present invention provides a genetically modified cell or non-human organism comprising such cells comprising modified genetic material which when expressed produces a polypeptide co-expressed with a reporter molecule and wherein the polypeptide is associated with terminal differentiation of a haematopoietic cell. Preferably, the genetic material gene is a Blimp allele or a part, fragment or functional form thereof. Furthermore, the identification of the reporter molecule in B-cell lineage cells indicates that such cells are committed to differentiate or have differentiated into ASC. Alternatively, reporter molecule activity in cells of a T cell lineage indicates that these cells are activated. Thus, as described herein, the presence of Blimp in a lymphocyte indicates that the cell is terminally differentiated or is committed to terminal differentiation. Exemplary T-cells include CD4+ T-cells and CD8+ T-cells and exemplary B-cells are ASC.

Abstract: The present invention provides animal model systems for cartilage-degenerative disease, which comprise transgenic animals which can express recombinant matrix-degrading enzymes (MDEs), particularly matrix metalloproteinases (MMPs), in a temporally and spatially regulated manner. The invention also provides methods for producing phenotypic indicators of cartilage-degenerative disease in a mammal and methods for determining the potential of a composition to counteract cartilage-degenerative disease. The invention also provides isolated nucleic acids encoding proMMP polypeptides that exhibit constitutive enzymatic activity and isolated proMMP polypeptides.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: Compositions useful for inhibiting the growth of bacteria, including bacteria that can cause gastric ulcers, are provided. In addition, transgenic organism that can produce such compositions are provided. Methods of using the compositions to treat or prevent gastric ulcers in a subject, including a human subject, also are provided.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: The present invention relates to the use of the digestive tract of an animal as a bioreactor for the production of a product of interest.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: A method of reconstituting an animal embryo involves transferring a diploid nucleus into an oocyte which is arrested in the metaphase of the second meiotic division. The oocyte is not activated at the time of transfer, so that the donor nucleus is kept exposed to the recipient cytoplasm for a period of time. The diploid nucleus can be donated by a cell in either the G0 or G1 phase of the cell cycle at the time of transfer. Subsequently, the reconstituted embryo is activated. Correct ploidy is maintained during activation, for example, by incubating the reconstituted embryo in the presence of a microtubule inhibitor such as nocodazole. The reconstituted embryo may then give rise to one or more live animal births. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: The present invention features compositions (e.g, nucleic acids encoding fat-1, optionally and operably linked to a constitutively active or tissue-specific promoter or other regulatory sequence and pharmaceutically acceptable formulations including that nucleic acid or biologically active variants thereof) and methods that can be used to effectively modify the content of PUFAs in animal cells (i.e., cells other than those of C. elegants, for example, mammalian cells such as myocytes, neurons (whether of the periferal or central nervous system), adipocytes, endothelial cells, and cancer cells). The modified cells, whether in vivo or ex vivo (e.g., in tissue culture), transgenic animals containing them, and food products obtained from those animals (e.g., meat or other edible parts of the animals (e.g., liver, kidney, or sweetbreads)) are also within the scope of the present invention.

Abstract: A method of reconstituting an animal embryo involves transferring the nucleus from a quiescent donor cell into a suitable recipient cell. The donor cell is quiescent, in that it is caused to exit from the growth and division cycle at G1 and to arrest in the G0 state. Nuclear transfer may take place by cell fusion. The reconstituted embryo may then give rise to one or more animals. The invention is useful in the production of transgenic animals as well as non-transgenics of high genetic merit.

Abstract: The present invention provides methods of producing transgenic livestock animals. The methods generally involve first introducing a nucleoprotein made up of nucleic acid and a recombinase into a totipotent or pluripotent cell to produce a recombinant totipotent or pluripotent cell and then growing the recombinant totipotent or pluripotent cell to produce the transgenic livestock animal. The invention further provides kits for use in generating transgenic non-human animals of the invention.

Abstract: The present invention relates to animals that express exogenous growth factors in their milk, and in particular to pigs that express exogenous IGF-I in their milk. The present invention also relates to methods for increasing piglet weight gain and intestinal lactase activity. The present invention thus provides a method of facilitating piglet development and decreasing piglet mortality.

Abstract: Disclosed is a method for the recombinant production of biofilaments, such as spider silk or insect fibroins, using transgenic animals which secrete the biofilaments in their milk and/or urine, and transgenic cells which secrete the biofilaments into culture media. Such a method is useful for producing large quantities of biofilament material. Also disclosed is a nucleic acid molecule for generating such transgenic animals.

Abstract: The invention provides transgenic nonhuman mammals expressing C1 inhibitor in their milk. The C1 inhibitor is useful in treating patients with hereditary angioedema or patients requiring immunosuppression.

Abstract: A process for the production of a peptide is disclosed, the process comprising expressing in the milk of a transgenic, non-human, placental mammal a fusion protein which comprises the peptide to be expressed linked to a fusion partner protein which is lysozyme. The fusion protein may be separate from the milk and cleaved to yield the target peptide. A transgenic, non-human, placental mammal whose genome incorporates a DNA molecule comprising a coding sequence encoding lysozyme coupled to a peptide is also described.

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 invention relates to the stabilization of milk from transgenic animals. In particular, the invention relates to the protection of proteins (e.g. fibrinogen) expressed in milk from transgenic animals by co-expression of a serine proteinase inhibitor (e.g., ?1-antitrypsin) in the milk of the transgenic animals.

Abstract: The present invention relates to novel alternative forms of human acetylcholinesterase (AChE) and nucleotide sequences encoding the same. The genes encoding the novel forms of human AChE have been identified in various malignant tumor cells. In a further aspect, the invention relates to a transgenic animal assay system for evaluating efficacy of drugs against cholinergic proteins, prior to or in the course of therapeutic treatment. Transgenic animals, preferably developing tadpole of Xenopus or mice which express human AChE, are used. The transgenic animal assay system is also useful for evaluating the toxicity of substances which potentially block human AChE (e.g. organophosphorous compounds).

Abstract: A transgenic, non-human mammalian animal is capable of expressing a heterologous gene for human or other recombinant physiologically functional fibrinogen holoprotein or individual subunit chain polypeptides thereof or a modified or fusion fibrinogen in mammary glands of the animals and secreting the expressed product into a body fluid. Methodology employing such a mammal yields recombinant physiologically functional fibrinogens, subunit chain polypeptides thereof, and modified or fusion fibrinogens.

Abstract: The present invention provides methods of producing a cloned non-human mammalian nuclear transfer (NT) embryo and methods for producing a cloned non-human mammal. Embodiments of the methods include introducing donor genetic material into a metaphase I oocyte; introducing donor genetic material into a non-enucleated oocyte; introducing donor genetic material obtained from a donor cell that is at metaphase into an oocyte; introducing donor genetic material into an oocyte, and naturally activating the oocyte or the NT embryo; and introducing donor genetic material obtained from a donor cell that is at late G1 phase into an oocyte.

Abstract: The present invention provides a substantially purified growth differentiation factor (GDF) receptor, including a GDF-8 (myostatin) receptor, as well as functional peptide portions thereof. In addition, the invention provides a virtual representation of a GDF receptor or a functional peptide portion thereof. The present invention also provides a method of modulating an effect of myostatin on a cell by contacting the cell with an agent that affects myostatin signal transduction in the cell. In addition, the invention provides a method of ameliorating the severity of a pathologic condition, which is characterized, at least in part, by an abnormal amount, development or metabolic activity of muscle or adipose tissue in a subject, by modulating myostatin signal transduction in a muscle cell or an adipose tissue cell in the subject.

Abstract: The invention relates to recombinant DNA constructs, a method for producing a recombinant biologically active protein in vivo in the urine of a non-human mammal using a kidney-specific promoter, such as the uromodulin promoter, and the transgenic non-human mammals that serve as urine-based bioreactors for protein production.

Abstract: Genetic transformation of a zygote and the embryo and mature organism which result therefrom is obtained by placing or inserting exogenous genetic material into the nucleus of the zygote or into any genetic material which ultimately forms at least a part of the nucleus of the zygote. It is preferred that the exogenous genetic material be added to a pronuclei of the zygote and is particularly preferred that it be added to the male pronucleus of the zygote. Thereafter, the zygote is allowed to undergo differentiation and development into the organism. The genotype of the zygote and the organism which results therefrom will include the genotype of the exogenous genetic material and the exogenous genetic material will be phenotypically expressed. The invention can be utilized in a variety of ways including, for example, animal and plant breeding to modify or create new species, it can be used in epigenetics and in the understanding and treatment of genetic diseases.

Abstract: Transgenic rats are generated which incorporate a primate B1 bradykinin receptor transgene(s) into their genome. This B1 bradykinin receptor gene is expressed in these transgenic rats, which results in binding of compounds which are selective for the primate form (such as the human form) of the receptor and not the rat form of the receptor. Therefore, the expressed transgenes within these transgenic lines mimic antagonist and agonist selectivity of the wild type primate B1 bradykinin receptor. These transgenic animals are useful as a specific receptor occupancy model for modulators of the B1 bradykinin receptor from the human or closely related species, as well as providing for an animal model system for assessment of the pharmacodynamic properties of such a B1 bradykinin modulator(s).

Abstract: The subject invention relates to a method of creating a cloned animal having the precise immunological response and capabilities as the founder animal.

Abstract: The subject invention relates to a method of transferring a specific immune response into a cloned animal. In this manner, one may create a specific, selective, secondary immune response in an otherwise immunologically naïve animal.

Abstract: Methods for the activation of nuclear transferred embryos using elevated calcium levels introduced into cells, and a maturation promoting factor (MPF) inhibitor are described. Elevated calcium levels introduced into the embryo cells from a culture medium containing elevated calcium levels, in the range 2 mM to about 12 mM, followed directly and immediately by incubation with DMAP are described. Also described are animals produced from embryos so treated.

Abstract: Production of proteins not normally secreted through conventional pathways such as membrane proteins including, for example, CFTR associated with cystic fibrosis, is now made possible by collection of such protein from the milk of lactating transgenic animals.

Abstract: The present invention concerns transgenic vertebrates that are useful in expressing proteins and in producing antibodies. The present invention discloses methods for producing vertebrates that are transgenic for a bacteriophage RNA polymerase. The present invention further discloses methods for the use of such transgenic vertebrates in protein expression and in antibody production.

Abstract: The present invention relates to a method of improving development potential of an embryo, embryos developed therefrom and organisms resulting from embryos developed from the method. In a first aspect of the present invention, there is provided a method of culturing an embryo to improve development potential, said method comprising; obtaining an embryo; and culturing the embryo to enhance trophectoderm development of the embryo. The method relates to improving the chances of an embryo implanting to result in a successful pregnancy. The embryos desirably become implantation competent favouring foetal-maternal interaction and development to term of an embryo. The trophectoderm stimulating agent may be any compound which is proven to stimulate normal trophectoderm development. Preferably the agent is fibroblast growth factor-4 (FGF4) protein.

Abstract: The present invention makes available powerful tools for the study of cancer, based on a novel expression construct for a constitutively active hydrocarbon receptor CA-AhR. The invention further comprises transgenic non-human animals, preferably mammals, expressing CA-AhR in one or more tissues thereof. An animal model based on the transgenic non-human animals forms the basis for novel methods e.g. for the study of cancer; for the screening of compounds, such as drug candidates; for the investigation of the molecular mechanisms of cancer, in particular stomach cancer; for the investigation of the mechanisms of highly differentiated adenocarcinoma etc. Likewise, in vitro models based on transformed cells or cell lines, functionally incorporating the inventive construct are disclosed.

Abstract: A DNA sequence containing a gene encoding a protein, the gene being under the transcriptional control in the DNA sequence of a mammalian milk protein promoter which does not naturally control the transcription of the gene, such DNA sequence including DNA enabling secretion of the protein.

Abstract: The invention features novel methods for the production of large quantities of xenogenous antibodies, such as human antibodies. Preferably, this result is effected by inactivation of IgM heavy chain expression and, optionally, by inactivation of Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of xenogenous antibodies (e.g., non-bovine antibodies), preferably human antibodies.

Abstract: The present invention provides a method and materials for reproducing an immune response of a mammal against one or more antigens of interest. The method preferably involves cloning a founder mammal and producing an immune response in the clone that is substantially identical to the immune response of the founder animal to the antigen or antigens of interest. Accordingly, a source of valuable antibodies can be maintained despite the death or illness of the antibody producing animal.

Abstract: The invention relates to an animal model of cancer. The animal carries a tumour xenograft and is immunosuppressed by administration of cyclosporin and ketoconazole. The model is useful for studying cancer and treatment thereof.

Abstract: The present invention relates to animals that express exogenous growth factors in their milk, and in particular to pigs that express exogenous IGF-I in their milk. The present invention also relates to methods for increasing piglet weight gain and intestinal lactase activity. The present invention thus provides a method of facilitating piglet development and decreasing piglet mortality.

Abstract: The invention provides transgenic nonhuman mammals producing phosphorylated lysosomal proteins in their milk, and methods of generating the same. Phosphorylation occurs at the 6′ position of a mannose side chain residue. Also provided are methods of purifying lysosomal proteins from milk, and incorporating the proteins into pharmaceutical compositions for use in enzyme replacement therapy.

Abstract: Methods of reducing the excitability of an excitable cell by transforming an excitable cell with a nucleic acid construct encoding an open rectifier K+ channel (dORK) (SEQ ID NO:2) or a modified open rectifier K+ channel (dORK&Dgr;) (SEQ ID NO:4), and expressing the open rectifier K+ channel in the excitable cell, wherein the excitability of the transformed cell is reduced. Also featured are transgenic animals expressing dORK or dORK&Dgr;.

Abstract: An improved method of nuclear transfer involving the transplantation of differentiated donor cell nuclei into enucleated oocytes of a species different from the donor cell is provided. The resultant nuclear transfer units are useful for the production of isogenic embryonic stem cells, in particular human isogenic embryonic or stem cells. These embryonic or stem-like cells are useful for producing desired differentiated cells and for introduction, removal or modification, of desired genes, e.g., at specific sites of the genome of such cells by homologous recombination. These cells, which may contain a heterologous gene, are especially useful in cell transplantation therapies and for in vitro study of cell differentiation. Also, methods for improving nuclear transfer efficiency by genetically altering donor cells to inhibit apoptosis, select for a specific cell cycle and/or enhance embryonic growth and development are provided.

Abstract: This invention includes methods for producing non-human mammals expressing monoclonal or oligoclonal B or T lymphocytes, as well as embryonic and hematopoietic stem cells that differentiate into monoclonal or oligoclonal B or T cells, using cloning by nuclear transfer with a B or T cell of interest as the nuclear donor cell.

Abstract: The invention discloses chimeric milk-producing tissues containing human mammary cells implanted into cleared mammary fat pad tissue or other suitable tissue of a non-human animal host, and discloses the use of human milk produced by chimeric milk-producing tissues. The invention further provides methods for avoiding problems of xenogeneic transplantation in chimeric milk-producing tissues.