Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: Disclosed herein are methods and compositions for performing assays for determining efficacy of drugs using rat SCID models that exhibit excellent take rates, and excellent tumor growth rates. The methods and compositions offer dramatically improved efficiencies compared to corresponding mouse equivalents.

Abstract: The instant application discloses methods of treating, reducing, or preventing pain in a mammal, which may include administering a compound capable of modulating a transient receptor potential channel. In one aspect, the TRP channel may be TRPC4. Types of pain contemplated by the present disclosure include acute, chronic, neuropathic, and nociceptive pain.

Abstract: The instant application discloses methods of treating, reducing, or preventing pain in a mammal, which may include administering a compound capable of modulating a transient receptor potential channel. In one aspect, the TRP channel may be TRPC4. Types of pain contemplated by the present disclosure include acute, chronic, neuropathic, and nociceptive pain.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: Disclosed are non-human mammals having a modified liver and methods of making such non-human mammals having a modified liver. The modified liver may be characterized by a non-germline, stable integration of a non-endogenous gene targeted to the liver of the non-human mammal. In certain aspects, the modified liver may have greater than at least 30% ablation of the endogenous hepatocyte population of the non-human mammal. In certain aspects, the non-human mammal may comprise at least 30% non-endogenous hepatocytes. The disclosed non-human mammals may be useful for pharmacology, drug absorption, distribution, metabolism, and excretion studies, collectively ADME and toxicology studies (ADME-tox), and/or drug screening.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in altered nervous system function. In one aspect, the altered function results in pain in the mammal. In another aspect, the nervous system dysfunction results in prolonged hyperalgesia, allodynia, and loss of sensory function. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of altered nervous system function mediated pain and methods of their use. In another aspect, the genetically modified rats, as well as the descendants and ancestors of such animals, are animal models of nervous system dysfunction resulting in prolonged hyperalgesia, allodynia, and loss of sensory function and methods of their use.

Abstract: The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to drug transport sensitivity or resistance drug transport resistance or sensitivity. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug transporter gene such as the Slc7a11 (NC_005101.2) gene, the Abcb1 (NC_005103.2) gene, etc. The present invention also provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to drug transport sensitivity or resistance drug transport resistance or sensitivity. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug transporter gene.

Abstract: The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to alterations in drug and chemical metabolism by modification of its structure or mechanism. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug metabolism gene such as the Cyp7b1 gene, the Cyp3a4 gene, etc. In another embodiment, the rat cell is a somatic cell. The inactivation of at least one drug metabolism allele results in an animal with a higher susceptibility to altered drug and chemical metabolism. In one embodiment, the genetically altered animal is a rat of this type and is able to serve as a useful model for altered drug and chemical metabolism or toxicology and as a test animal for autoimmune and other studies. The invention additionally pertains to the use of such rats or rat cells, and their progeny in research and medicine.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in altered nervous system function. In one aspect, the altered function results in pain in the mammal. In another aspect, the nervous system dysfunction results in prolonged hyperalgesia, allodynia, and loss of sensory function. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of altered nervous system function mediated pain and methods of their use. In another aspect, the genetically modified rats, as well as the descendants and ancestors of such animals, are animal models of nervous system dysfunction resulting in prolonged hyperalgesia, allodynia, and loss of sensory function and methods of their use.

Abstract: The present invention provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to drug transport sensitivity or resistance drug transport resistance or sensitivity. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug transporter gene such as the Slc7a11 (NC_005101.2) gene, the Abcb1 (NC_005103.2) gene, etc. The present invention also provides a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to drug transport sensitivity or resistance drug transport resistance or sensitivity. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a drug transporter gene.

Abstract: The instant application discloses methods of treating, reducing, or preventing pain in a mammal, which may include administering a compound capable of modulating a transient receptor potential channel. In one aspect, the TRP channel may be TRPC4. Types of pain contemplated by the present disclosure include acute, chronic, neuropathic, and nociceptive pain.

Abstract: This invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of tumor suppressor gene(s) or gene product(s). In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human cancer and methods of their use.

Abstract: This invention relates to a genetically modified or chimeric rat cell whose genome comprises chromosomal alleles of an obesity-diabetes gene (especially, the Mc4r gene or Lep gene), wherein at least one of the two alleles contains a mutation, or the progeny of this cell. The obesity or diabetes gene may affect any of the pathways of obesity and diabetes. The obesity or diabetes gene may predispose the rat to a phenotype of obese and diabetic, lean and diabetic, obese and non-diabetic, non-obese and diabetic or any of the combinations thereof. In another aspect, the invention relates to a desired rat or a rat cell which contains a predefined, specific and desired alteration rendering the rat or rat cell predisposed to obesity or diabetes.

Abstract: The present invention relates to the engineering of animal cells, preferably mammalian, more preferably rat, that are deficient due to the disruption of gene(s) or gene product(s) resulting in cytokine-cytokine mediated autoimmune and inflammatory disease. In another aspect, the invention relates to genetically modified rats, as well as the descendants and ancestors of such animals, which are animal models of human autoimmune and inflammatory disease and methods of their use. Specifically, the invention pertains to a genetically altered rat, or a rat cell in culture, that is defective in at least one of two alleles of a cytokine gene such as the Faslg gene, the Fas gene, etc. In one embodiment, the cytokine gene is the Faslg gene. In another embodiment, the cytokine gene is one of several known cytokine genes, such as Fas, IFN?, TNF-?, IL-2, IL-10, and IL-12.