公开(公告)号：US20130150465A1

公开(公告)日：2013-06-13

申请号：US13592045

申请日：2012-08-22

申请人： Peter Michael Kragh ,  Lars Axel Bolund ,  Charlotte Brandt Sørensen ,  Thomas Juhl Corydon ,  Niels Gregersen ,  Peter Bross

发明人： Peter Michael Kragh ,  Lars Axel Bolund ,  Charlotte Brandt Sørensen ,  Thomas Juhl Corydon ,  Niels Gregersen ,  Peter Bross

IPC分类号： A01K67/027

CPC分类号： A01K67/0275 ,  A01K67/0271 ,  A01K2217/052 ,  A01K2227/108 ,  A01K2267/0331 ,  C12N15/8509 ,  C12N15/8778 ,  C12N2800/30 ,  C12N2800/90

摘要： The present invention relates to a genetically modified pig as a model for studying breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex. The modified pig model displays one or more phenotypes associated with any of said disorders. Disclosed is also a modified pig comprising a modified endogeneous BRCA1 and/or BRCA2 gene, and/or a modified ornithine transcarbamylase gene, and/or a modified Keratin 14 gene and/or a transcriptional or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex are disclosed.

摘要翻译： 本发明涉及一种转基因猪作为研究乳腺癌，线粒体相关蛋白折叠病和/或大疱性表皮松解症的模型。 修改的猪模型显示与任何所述疾病相关的一种或多种表型。 还公开了包含修饰的内源性BRCA1和/或BRCA2基因和/或修饰的鸟氨酸转氨酶基因和/或修饰的角蛋白14基因和/或转录或翻译产物或其部分的修饰的猪。 本发明还涉及生产改性猪的方法; 以及用于评估乳腺癌，线粒体相关蛋白折叠病和/或大疱性表皮松解症的治疗效果的评价方法。 用于筛选药物组合物的功效的方法; 公开了一种治疗患有乳腺癌，线粒体相关蛋白折叠病和/或大疱表皮松解症的人的方法。

公开(公告)号：US08581021B2

公开(公告)日：2013-11-12

申请号：US12529958

申请日：2008-03-07

申请人： Jacob Giehm Mikkelsen ,  Brian Moldt ,  Anders Lade Nielsen ,  Lars Axel Bolund ,  Peter Michael Kragh ,  Jannik Ejnar Jakobsen ,  Arne Lund Jørgensen

发明人： Jacob Giehm Mikkelsen ,  Brian Moldt ,  Anders Lade Nielsen ,  Lars Axel Bolund ,  Peter Michael Kragh ,  Jannik Ejnar Jakobsen ,  Arne Lund Jørgensen

IPC分类号： A01K67/00 ,  C12N15/00

CPC分类号： A01K67/0275 ,  A01K67/0273 ,  A01K2217/05 ,  A01K2227/108 ,  A01K2267/035 ,  C12N15/8509 ,  C12N15/8778 ,  C12N2800/30 ,  C12N2800/90 ,  C12N2840/203

摘要： The present invention relates to a genetically modified pig comprising at least one site for integration of at least one transgene. The invention also pertains to a porcine embryo, blastocyst, fetus, donor cell and/or cell nucleus, derived from said genetically modified pig. In another aspect, the invention relates to any genetically modified porcine blastocyst, wherein the genetically modified genome comprises at least one site for integration of at least one transgene.

摘要翻译： 本发明涉及包含至少一个用于整合至少一个转基因的位点的转基因猪。 本发明还涉及源自所述转基因猪的猪胚，胚泡，胎儿，供体细胞和/或细胞核。 另一方面，本发明涉及任何遗传修饰的猪胚泡，其中所述经遗传修饰的基因组包含至少一个用于整合至少一个转基因的位点。

公开(公告)号：US20100154069A1

公开(公告)日：2010-06-17

申请号：US12529958

申请日：2008-03-07

申请人： Jacob Giehm Mikkelsen ,  Brian Moldt ,  Anders Lade Nielsen ,  Lars Axel Bolund ,  Peter Michael Kragh ,  Jannik Ejnar Jakobsen ,  Arne Lund Jørgensen

发明人： Jacob Giehm Mikkelsen ,  Brian Moldt ,  Anders Lade Nielsen ,  Lars Axel Bolund ,  Peter Michael Kragh ,  Jannik Ejnar Jakobsen ,  Arne Lund Jørgensen

IPC分类号： A01K67/027 ,  C12N5/10 ,  C12N15/85 ,  C12N15/09 ,  A01K67/02

CPC分类号： A01K67/0275 ,  A01K67/0273 ,  A01K2217/05 ,  A01K2227/108 ,  A01K2267/035 ,  C12N15/8509 ,  C12N15/8778 ,  C12N2800/30 ,  C12N2800/90 ,  C12N2840/203

摘要： The present invention relates to a genetically modified pig comprising at least one site for integration of at least one transgene. The invention also pertains to a porcine embryo, blastocyst, foetus, donor cell and/or cell nucleus, derived from said genetically modified pig. In another aspect, the invention relates to any genetically modified porcine blastocyst, wherein the genetically modified genome comprises at least one site for integration of at least one transgene.

摘要翻译： 本发明涉及包含至少一个用于整合至少一个转基因的位点的转基因猪。 本发明还涉及源自所述转基因猪的猪胚，胚泡，胎儿，供体细胞和/或细胞核。 另一方面，本发明涉及任何遗传修饰的猪胚泡，其中所述经遗传修饰的基因组包含至少一个用于整合至少一个转基因的位点。

公开(公告)号：US08546643B2

公开(公告)日：2013-10-01

申请号：US12529955

申请日：2008-03-06

申请人： Jacob Fog Bentzon ,  Charlotte Brandt Sørensen ,  Peter Michael Kragh ,  Jacob Giehm Mikkelsen ,  Erling Falk ,  Lars Axel Bolund ,  Thomas Juhl Corydon

发明人： Jacob Fog Bentzon ,  Charlotte Brandt Sørensen ,  Peter Michael Kragh ,  Jacob Giehm Mikkelsen ,  Erling Falk ,  Lars Axel Bolund ,  Thomas Juhl Corydon

IPC分类号： A01K97/00 ,  A01K67/027 ,  C12N15/00

CPC分类号： C12N15/8509 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2227/108 ,  A01K2267/0362 ,  C12N15/8778 ,  C12N2799/025 ,  C12N2800/30 ,  C12N2800/90

摘要： The present invention relates to a genetically modified pig as a model for studying atherosclerosis. The modified pig model displays one or more phenotypes associated with atherosclerosis. Disclosed is also a modified pig comprising a mutation in the endogenous ApoE gene or part thereof, LDL gene or part thereof, LDL receptor gene, or transcriptional or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of atherosclerosis; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from atherosclerosis are disclosed.

摘要翻译： 本发明涉及作为研究动脉粥样硬化的模型的转基因猪。 修改的猪模型显示与动脉粥样硬化相关的一种或多种表型。 还公开了包含内源性ApoE基因或其部分，LDL基因或其部分，LDL受体基因或转录或翻译产物或其部分的突变的修饰猪。 本发明还涉及生产改性猪的方法; 以及用于评估动脉粥样硬化的治疗效果的方法; 用于筛选药物组合物的功效的方法; 并且公开了治疗患有动脉粥样硬化的人的方法。

公开(公告)号：US20100122356A1

公开(公告)日：2010-05-13

申请号：US12529812

申请日：2008-03-07

申请人： Peter Michael Kragh ,  Lars Axel Bolund ,  Karsten Kristiansen ,  Charlotte Brandt Sørensen ,  Jacob Giehm Mikkelsen ,  Nicklas Heine Staunstrup ,  Thomas Kongstad Petersen ,  Lars Svensson

发明人： Peter Michael Kragh ,  Lars Axel Bolund ,  Karsten Kristiansen ,  Charlotte Brandt Sørensen ,  Jacob Giehm Mikkelsen ,  Nicklas Heine Staunstrup ,  Thomas Kongstad Petersen ,  Lars Svensson

IPC分类号： A61K49/00 ,  A01K67/027 ,  C12N5/10 ,  C12N15/63 ,  A61P17/06

CPC分类号： A01K67/0273 ,  A01K2207/15 ,  A01K2217/00 ,  A01K2227/108 ,  A01K2267/0325 ,  C12N15/8778 ,  C12N2517/04 ,  C12N2800/30 ,  C12N2800/90 ,  G01N2500/00

摘要： The present invention relates to a genetically modified pig as a model for studying psoriasis. The modified pig model displays one or more phenotypes associated with psoriasis. Disclosed is also a modified pig comprising a mutation in the endogenous ILK-I Ra, JunB/cJun, CD18, IKK2, and/or LIG1 gene, and/or a human, porcine and/or murine PPARs, PPAR-δ, lκB-α, STAT3c, Integrin beta 1, Integrin alpha 2, MEK1, Amphiregulin, BMP-6, VEGF, JunBΔec-JunΔep, IL-I a, TGF.beta 1, CD18 hypo, Cre/lkk2FL/FL, Dsg1, SCCE, TGF-a, TNF-a, IL-20, IFN-g, LIG1 KO, KGF, IL-6, PAFR1 Cre/lkk2FL/FL, IL1 R, Dsg3, IFN-gamma, p40, ILI Ra, IKK2, JunB/c-Jun, and/or LIG1 gene, transcriptional and/or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of psoriasis, for screening the efficacy of a pharmaceutical composition, and a method for treatment of human being suffering from psoriasis are disclosed.

摘要翻译： 本发明涉及一种转基因猪作为研究牛皮癣的模型。 修改后的猪模型显示与牛皮癣相关的一种或多种表型。 还公开了包含内源性ILK-IRa，JunB / cJun，CD18，IKK2和/或LIG1基因和/或人，猪和/或鼠PPARs，PPAR-δ， B-α，STAT3c，整合素β1，整合素α2，MEK1，Amphiregulin，BMP-6，VEGF，JunB＆Dgr; ec-Jun＆Dgr; ep，IL-1α，TGFβ1，CD18 hypo，Cre / lkk2FL / FL ，Dsg1，SCCE，TGF-α，TNF-α，IL-20，IFN-g，LIG1KO，KGF，IL-6，PAFR1 Cre / Ikk2FL / FL，IL1R，Dsg3，IFN-γ，p40， ，IKK2，JunB / c-Jun和/或LIG1基因，转录和/或翻译产物或其一部分。 本发明还涉及生产改性猪的方法; 公开了用于评价银屑病治疗效果，用于筛选药物组合物的功效以及治疗患有牛皮癣的方法的方法。

公开(公告)号：US08513486B2

公开(公告)日：2013-08-20

申请号：US12066169

申请日：2006-09-08

申请人： Yutao Du ,  Lars Axel Bolund ,  Gabor Vajta ,  Peter Michael Kragh

发明人： Yutao Du ,  Lars Axel Bolund ,  Gabor Vajta ,  Peter Michael Kragh

IPC分类号： C12N15/00 ,  C12N15/02

CPC分类号： C12N15/877 ,  A01K2217/05 ,  C12N15/8778

摘要： The present invention discloses methods for cell nuclear transfer that comprise for example modification of zona pellucida of an oocyte, and/or sectioning of oocytes into several parts. The present invention also discloses methods for producing a genetically modified non-human mammal. Genetically modified non-human mammals obtainable by the disclosed methods are also within the scope of the present invention. Disclosed are also methods for cryopreservation of cells.

摘要翻译： 本发明公开了用于细胞核转移的方法，其包括例如修饰卵母细胞的透明带，和/或将卵母细胞分成若干部分。 本发明还公开了用于生产遗传修饰的非人哺乳动物的方法。 通过公开的方法可获得的转基因非人哺乳动物也在本发明的范围内。 还公开了冷冻保存细胞的方法。

公开(公告)号：US20100115636A1

公开(公告)日：2010-05-06

申请号：US12529816

申请日：2008-03-06

申请人： Peter Michael Kragh ,  Lars Axel Bolund ,  Charlotte Brandt Sorensen ,  Thomas Juhl Corydon ,  Niels Gregersen ,  Peter Bross

发明人： Peter Michael Kragh ,  Lars Axel Bolund ,  Charlotte Brandt Sorensen ,  Thomas Juhl Corydon ,  Niels Gregersen ,  Peter Bross

IPC分类号： G01N33/00 ,  A01K67/00 ,  C12N15/00

CPC分类号： A01K67/0275 ,  A01K67/0271 ,  A01K2217/052 ,  A01K2227/108 ,  A01K2267/0331 ,  C12N15/8509 ,  C12N15/8778 ,  C12N2800/30 ,  C12N2800/90

摘要： The present invention relates to a genetically modified pig as a model for studying breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex. The modified pig model displays one or more phenotypes associated with any of said disorders. Disclosed is also a modified pig comprising a modified endogeneous BRCA1 and/or BRCA 2 gene, and/or a modified ornithine transcarbamylase gene, and/or a modified Keratin 14 gene and/or a transcriptional or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from breast cancer, mitochondria related protein folding disorders and/or epidermolysis bullosa simplex are disclosed.

摘要翻译： 本发明涉及一种转基因猪作为研究乳腺癌，线粒体相关蛋白折叠病和/或大疱性表皮松解症的模型。 修改的猪模型显示与任何所述疾病相关的一种或多种表型。 还公开了一种修饰的猪，其包含修饰的内源性BRCA1和/或BRCA2基因和/或修饰的鸟氨酸转氨酶基因，和/或修饰的角蛋白14基因和/或转录或翻译产物或其部分。 本发明还涉及生产改性猪的方法; 以及用于评估乳腺癌，线粒体相关蛋白折叠病和/或大疱性表皮松解症的治疗效果的评价方法。 用于筛选药物组合物的功效的方法; 公开了一种治疗患有乳腺癌，线粒体相关蛋白折叠病和/或大疱表皮松解症的人的方法。

公开(公告)号：US20110265192A1

公开(公告)日：2011-10-27

申请号：US13062028

申请日：2009-09-03

申请人： Lars Axel Bolund ,  Karsten Kristiansen ,  Jacob Giehm Mikkelsen ,  Nicklas Heine Staunstrup

发明人： Lars Axel Bolund ,  Karsten Kristiansen ,  Jacob Giehm Mikkelsen ,  Nicklas Heine Staunstrup

IPC分类号： G01N33/00 ,  C12N15/873 ,  A01K67/00 ,  A01K67/027 ,  C12N5/10 ,  C12Q1/68

CPC分类号： C12N15/8509 ,  A01K2217/052 ,  A01K2217/15 ,  A01K2217/206 ,  A01K2227/108 ,  A01K2267/03 ,  A01K2267/0393 ,  C07K14/721

摘要： A sensor system for detecting the activation of specific nuclear receptors in a tissue of an animal is provided. The nuclear receptor sensor system comprises a sensor component comprising a nuclear receptor or part thereof coupled to a DNA-binding domain, and a reporter component comprising a reporter gene. Transgenic animals, such as a transgenic pig is provided, which comprises the components of the nuclear receptor sensor system in its genome. Also methods of producing the transgenic animal is provided as well as use of the transgenic animal for evaluating the activity of a nuclear receptor in vivo.

摘要翻译： 提供了用于检测动物组织中的特定核受体活化的传感器系统。 核受体传感器系统包括包含核受体或其部分耦合至DNA结合结构域的传感器组分和包含报告基因的报道分子。 提供转基因动物，例如转基因猪，其包含其基因组中核受体传感器系统的组分。 还提供了产生转基因动物的方法以及转基因动物用于评价体内核受体活性的用途。

公开(公告)号：US20100138939A1

公开(公告)日：2010-06-03

申请号：US12529955

申请日：2008-03-06

申请人： Jacob Fog Bentzon ,  Charlotte Brandt Sørensen ,  Peter Michael Kragh ,  Jacob Giehm Mikkelsen ,  Erling Falk ,  Lars Axel Bolund ,  Thomas Juhl Corydon

发明人： Jacob Fog Bentzon ,  Charlotte Brandt Sørensen ,  Peter Michael Kragh ,  Jacob Giehm Mikkelsen ,  Erling Falk ,  Lars Axel Bolund ,  Thomas Juhl Corydon

IPC分类号： A01K67/027 ,  C12N5/07 ,  A61K31/40 ,  A61P9/10

CPC分类号： C12N15/8509 ,  A01K67/0271 ,  A01K67/0275 ,  A01K2217/052 ,  A01K2227/108 ,  A01K2267/0362 ,  C12N15/8778 ,  C12N2799/025 ,  C12N2800/30 ,  C12N2800/90

摘要： The present invention relates to a genetically modified pig as a model for studying atherosclerosis. The modified pig model displays one or more phenotypes associated with atherosclerosis. Disclosed is also a modified pig comprising a mutation in the endogenous ApoE gene or part thereof and/or LDL gene or part thereof, and/or LDL receptor gene, and/or transcriptional and/or translational product or part thereof. The invention further relates to methods for producing the modified pig; and methods for evaluating the effect of a therapeutical treatment of atherosclerosis; methods for screening the efficacy of a pharmaceutical composition; and a method for treatment of a human being suffering from atherosclerosis are disclosed.

摘要翻译： 本发明涉及作为研究动脉粥样硬化的模型的转基因猪。 修改的猪模型显示与动脉粥样硬化相关的一种或多种表型。 还公开了包含内源性ApoE基因或其部分和/或LDL基因或其部分和/或LDL受体基因和/或转录和/或翻译产物或其部分的突变的修饰猪。 本发明还涉及生产改性猪的方法; 以及用于评估动脉粥样硬化的治疗效果的方法; 用于筛选药物组合物的功效的方法; 并且公开了治疗患有动脉粥样硬化的人的方法。

公开(公告)号：US20090119787A1

公开(公告)日：2009-05-07

申请号：US12066169

申请日：2006-09-08

申请人： Yutao Du ,  Lars Axel Bolund ,  Gabor Vajta ,  Peter Michael Kragh

发明人： Yutao Du ,  Lars Axel Bolund ,  Gabor Vajta ,  Peter Michael Kragh

IPC分类号： A01K67/027 ,  A01K67/00

CPC分类号： C12N15/877 ,  A01K2217/05 ,  C12N15/8778

摘要： The present invention discloses methods for cell nuclear transfer that comprise for example modification of zona pellucida of an oocyte, and/or sectioning of oocytes into several parts. The present invention also discloses methods for producing a genetically modified non-human mammal. Genetically modified non-human mammals obtainable by the disclosed methods are also within the scope of the present invention. Disclosed are also methods for cryopreservation of cells.

摘要翻译： 本发明公开了用于细胞核转移的方法，其包括例如修饰卵母细胞的透明带，和/或将卵母细胞分成若干部分。 本发明还公开了用于生产遗传修饰的非人哺乳动物的方法。 通过公开的方法可获得的转基因非人哺乳动物也在本发明的范围内。 还公开了冷冻保存细胞的方法。