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1. 发明授权

US07271311B2 Mammalian model for diabetes 失效
标题翻译：哺乳动物模型糖尿病
公开(公告)号：US07271311B2
公开(公告)日：2007-09-18
申请号：US10252111
申请日：2002-09-23
申请人： Fumitoshi Ishino , Naoki Miyoshi , Tomoko Ishino , Minesuke Yokoyama , Shigeharu Wakana
发明人： Fumitoshi Ishino , Naoki Miyoshi , Tomoko Ishino , Minesuke Yokoyama , Shigeharu Wakana
IPC分类号： G01N33/00 , A01K67/27 , A01K67/33
CPC分类号： C12N15/8509 , A01K67/0273 , A01K67/0275 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0306 , C07K14/4705
摘要： An object of the present invention is to provide a model mammal for diabetes onset, being useful for elucidating the onset mechanism of diabetes caused by a blockage of signal transduction from insulin, and for the development of a remedy for said diabetes, and to provide a screening method of a remedy for said diabetes. A diabetic-prone transgenic mouse is prepared in a process comprising the steps of: a transgene that contains a Meg1/Grb10 gene, an imprinted gene exhibiting maternal expression, or a human GRB10 gene in the downstream of a chicken β-actin promoter and in the upstream of a rabbit β-globin poly A is constructed, and subsequently the transgene is microinjected into a male proneucleus of a mouse fertilized egg; thus obtained egg cell is cultured and then transplanted into an oviduct of a pseudopregnant female mouse; after rearing up the recipient animal, baby mice that have the above-mentioned cDNA are selected from the mice born from the recipient animal.
摘要翻译：本发明的目的是提供一种用于糖尿病发作的模型哺乳动物，可用于阐明由胰岛素信号传导阻断引起的糖尿病发病机制，以及用于开发所述糖尿病的治疗方法，并提供一种所述糖尿病治疗方法的筛选方法。制备具有糖尿病倾向的转基因小鼠，该方法包括以下步骤：在鸡β-肌动蛋白启动子的下游含有Meg1 / Grb10基因，表达母体表达的印记基因或人GRB10基因的转基因构建了兔β-珠蛋白聚A的上游，随后将转基因显微注射入小鼠受精卵的雄性易位; 由此获得的卵细胞被培养，然后移植到假孕女性小鼠的输卵管中; 在饲养受体动物后，具有上述cDNA的婴儿小鼠选自从受体动物出生的小鼠。

2. 发明授权

US07067713B2 C1 Inhibitor produced in the milk of transgenic non-human mammals 有权
标题翻译： C1转基因非人哺乳动物乳中产生的抑制剂
公开(公告)号：US07067713B2
公开(公告)日：2006-06-27
申请号：US10181704
申请日：2001-01-31
申请人： Jan Henricus Nuijens , Henricus Antonius Van Veen , Frank Robert Pieper , Joris Jan Heus
发明人： Jan Henricus Nuijens , Henricus Antonius Van Veen , Frank Robert Pieper , Joris Jan Heus
IPC分类号： C12P21/00 , A01K67/27
CPC分类号： C07K14/8121 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/105 , A01K2227/107 , A01K2267/01 , A23C2230/05 , A61K38/00 , C12N15/8509
摘要： 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.
摘要翻译：本发明提供了在其乳中表达C1抑制剂的转基因非人哺乳动物。 C1抑制剂可用于治疗遗传性血管性水肿患者或需要免疫抑制的患者。

3. 发明授权

US07507872B2 Transgenic toll-like receptor 9 (TLR9) mice 有权
标题翻译：转基因toll样受体9（TLR9）小鼠
公开(公告)号：US07507872B2
公开(公告)日：2009-03-24
申请号：US10088567
申请日：2001-06-05
申请人： Shizuo Akira , Hiroaki Hemmi
发明人： Shizuo Akira , Hiroaki Hemmi
IPC分类号： A01K67/27 , C12N5/00
CPC分类号： C07K14/705 , A01K2217/075
摘要： The present invention provides a receptor protein specifically recognizing bacterial DNA having an unmethylated CpG sequence, a genomic DNA encoding it, an experimental animal model useful for examining responsiveness of a host immune cell against a bacterial infectious disease. DNA encoding a receptor protein specifically recognizing bacterial DNA having an unmethylated CpG sequence is screened by BLAST search, a number of EST clones having high homology with various TLRs is screened, these clones are used as a probe to isolate a full-length cDNA from mouse macrophage cDNA library, and the sequence of bases of the cDNA is analyzed to confirm that it is TLR9 comprising a conserved regions such as LRR and TIR regions, and then a knockout mouse is produced to confirm that TLR9 is a receptor protein of oligonucleotides having an unmethylated CpG sequence of bacterial DNA.
摘要翻译：本发明提供了特异性识别具有非甲基化CpG序列的细菌DNA的受体蛋白，编码它的基因组DNA，用于检测宿主免疫细胞对细菌感染性疾病的反应性的实验动物模型。通过BLAST检测筛选编码特异性识别具有未甲基化CpG序列的细菌DNA的受体蛋白质的DNA，筛选出与各种TLRs具有高同源性的许多EST克隆，将这些克隆作为探针从小鼠中分离全长cDNA 分析巨噬细胞cDNA文库和cDNA的碱基序列，以确认其是包含保守区域如LRR和TIR区域的TLR9，然后产生敲除小鼠，以证实TLR9是具有细菌DNA的未甲基化CpG序列。

4. 发明授权

US07378569B2 Transgenic pigs carrying both hHO-1 and hDAF transgenes for xenotransplantation 失效
标题翻译：携带hHO-1和hDAF转基因的转基因猪用于异种移植
公开(公告)号：US07378569B2
公开(公告)日：2008-05-27
申请号：US10857613
申请日：2004-06-01
申请人： Ching-Fu Tu , Chi-Kai Yang , Ming-Shing Liu , Lin-Lin Ho , Kuei-Feng Huang , Chun-Jean Lee , Hao-Chih Tai
发明人： Ching-Fu Tu , Chi-Kai Yang , Ming-Shing Liu , Lin-Lin Ho , Kuei-Feng Huang , Chun-Jean Lee , Hao-Chih Tai
IPC分类号： A01K67/27 , A01K67/033 , C12N5/00
CPC分类号： A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2227/108 , A01K2267/01
摘要： The invention provides a transgenic animal carrying two transgenes, one encoding a human decay accelerating factor (hDAF) and the other encoding a human heme oxygenase-1 (hHO)-1, which are useful for providing cells, tissues or organs therefrom for xenotransplantation.
摘要翻译：本发明提供了一种携带两种转基因的转基因动物，一种编码人衰变加速因子（hDAF），另一种编码人血红素加氧酶-1（hHO）-1），其用于从其中提供用于异种移植的细胞，组织或器官。

5. 发明授权

US07250551B2 Transgenic mice expressing inducible human p25 失效
标题翻译：表达诱导型人p25的转基因小鼠
公开(公告)号：US07250551B2
公开(公告)日：2007-07-31
申请号：US10625986
申请日：2003-07-24
申请人： Li-Huei Tsai , Ming-Sum Lee , Jonathan C. Cruz
发明人： Li-Huei Tsai , Ming-Sum Lee , Jonathan C. Cruz
IPC分类号： A01K67/27 , G01N33/00 , C12N15/00 , C12N5/00
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/0318 , A61K31/00 , A61K31/365 , A61K49/0008 , C07K2319/41 , C07K2319/60 , C12N15/8509 , C12N2710/16611 , C12N2710/16643 , C12N2830/00 , C12Q1/485 , G01N33/6896 , G01N2500/04 , G01N2800/2821
摘要： Disclosed are improved methods of treating individuals with Alzheimer's disease (AD) as well as methods to diagnose AD in an individual. Also included are compounds and methods of identifying compounds to treat AD. The present invention also discloses methods for decreasing the phosphorylation of amyloid precursor protein (APP), including inhibiting phosphorylation of amino acid residue tyrosine 668 of APP and for reducing cleavage of APP. The present invention further discloses transgenic (Tg), non-human animals and cells expressing a p25 transgene that are models of neurodegenerative diseases. Embodiments of the present invention are directed to methods wherein the Tg animals and Tg cells of the invention are used to screen for modulators of neurodegenerative disorders. The Tg animals and cells of the present invention are useful for elucidating the mechanisms of neurodegenerative disorders.
摘要翻译：公开了治疗患有阿尔茨海默病（AD）的个体的改进方法以及在个体中诊断AD的方法。还包括鉴定化合物以治疗AD的化合物和方法。本发明还公开了降低淀粉样蛋白前体蛋白（APP）的磷酸化的方法，包括抑制APP的氨基酸残基酪氨酸668的磷酸化和减少APP的切割。本发明还公开了转基因（Tg）非人动物和表达作为神经变性疾病模型的p25转基因的细胞。本发明的实施方案涉及其中本发明的Tg动物和Tg细胞用于筛选神经变性疾病的调节剂的方法。本发明的Tg动物和细胞可用于阐明神经变性疾病的机制。

6. 发明授权

US07126040B2 Mouse model for aging 有权
标题翻译：老鼠模型老化
公开(公告)号：US07126040B2
公开(公告)日：2006-10-24
申请号：US11119099
申请日：2005-04-29
申请人： Tomas A. Prolla , Gregory C. Kujoth
发明人： Tomas A. Prolla , Gregory C. Kujoth
IPC分类号： A01K67/27 , G01N33/00
CPC分类号： A01K67/0275 , A01K2217/05 , A01K2267/03
摘要： A mouse model for mammalian aging is disclosed. In one embodiment, the invention comprises a mouse having a genomic mutation in the exonuclease domain II (ExoII) of a mitochondrial DNA polymerase gamma (PolG) gene, wherein the mutation leads to high levels of mutations in polymerase mtDNA.
摘要翻译：公开了哺乳动物老化的小鼠模型。在一个实施方案中，本发明包括在线粒体DNA聚合酶γ（PolG）基因的外切核酸酶结构域II（ExoII）中具有基因组突变的小鼠，其中突变导致聚合酶mtDNA中的高水平突变。

7. 发明授权

US07074983B2 Transgenic bovine comprising human immunoglobulin loci and producing human immunoglobulin 有权
标题翻译：包含人免疫球蛋白基因座并产生人免疫球蛋白的转基因牛
公开(公告)号：US07074983B2
公开(公告)日：2006-07-11
申请号：US09988115
申请日：2001-11-16
申请人： James M. Robl , Richard A. Goldsby , Stacy E. Ferguson , Yoshimi Kuroiwa , Kazuma Tomizuka , Isao Ishida , Barbara A. Osborne
发明人： James M. Robl , Richard A. Goldsby , Stacy E. Ferguson , Yoshimi Kuroiwa , Kazuma Tomizuka , Isao Ishida , Barbara A. Osborne
IPC分类号： A01K67/27 , C12P21/00 , A61K38/00
CPC分类号： A01K67/0273 , A01K67/0276 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2217/075 , A01K2227/101 , A01K2267/01 , C12N9/1051 , C12N15/8509 , C12N2800/30
摘要： The present invention relates to the production of a transgenic bovine which comprises a genetic modification that results in inactivation and loss of expression of its endogenous antibodies, and the expression of xenogenous antibodies, preferably human antibodies. This is effected by inactivation of the IgM heavy chain expression and, optionally, by inactivation of the Ig light chain expression, and by the further introduction of an artificial chromosome which results in the expression of non-bovine antibodies, preferably human antibodies.
摘要翻译：本发明涉及转基因牛的生产，其包含导致其内源性抗体失活和丧失表达的遗传修饰，以及异源抗体，优选人抗体的表达。这通过IgM重链表达的失活和任选地通过Ig轻链表达的失活以及进一步引入导致非牛抗体（优选人抗体）表达的人造染色体来实现。

8. 发明授权

US07169963B2 Mammals expressing IGF-1 and alpha-lactalbumin in their milk 有权
标题翻译：在其牛奶中表达IGF-1和α-乳清蛋白的哺乳动物
公开(公告)号：US07169963B2
公开(公告)日：2007-01-30
申请号：US10676566
申请日：2003-09-30
申请人： Matthew B. Wheeler , Sharon M. Donovan , Gregory T. Bleck , Marcia Monaco-Siegel
发明人： Matthew B. Wheeler , Sharon M. Donovan , Gregory T. Bleck , Marcia Monaco-Siegel
IPC分类号： A01K67/27 , C12P21/00
CPC分类号： C07K14/76 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2227/108 , A01K2267/01 , A01K2267/02 , A23C2230/05 , C07K14/65 , C12N15/8509 , C12N2830/008 , C12N2830/85
摘要： 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.
摘要翻译：本发明涉及在其乳中表达外源生长因子的动物，特别涉及在其乳中表达外源性IGF-I的猪。本发明还涉及增加仔猪体重增加和肠内乳糖酶活性的方法。因此，本发明提供了促进仔猪发育和降低仔猪死亡率的方法。

9. 发明授权

US07161057B2 Animal model having a chimeric human liver 有权
公开(公告)号：US07161057B2
公开(公告)日：2007-01-09
申请号：US10243087
申请日：2002-09-12
申请人： Norman M. Kneteman , D. Lorne Tyrrell , David F. Mercer
发明人： Norman M. Kneteman , D. Lorne Tyrrell , David F. Mercer
IPC分类号： G01N33/00 , A01K67/27 , A01K67/00 , A01K67/33
CPC分类号： C12N15/8509 , A01K67/0271 , A01K67/0275 , A01K2217/05 , A01K2227/105 , A01K2267/03 , A01K2267/0337 , C07K14/765 , C12N9/6424 , C12N15/63
摘要： The present invention features a non-human animal model that is susceptible to infection by human hepatotrophic pathogens, particularly human hepatitis C virus (HCV). The model is based on a non-human, immunocompromised transgenic animal having a human-mouse chimeric liver, where the transgene provides for expression of a urokinase-type plasminogen activator in the liver. The invention also features methods for identifying candidate therapeutic agents, e.g., agents having antiviral activity against HCV infection. The animals of the invention are also useful in assessing toxicity of various agents, as well as the activity of agents in decreasing blood lipids.

10. 发明授权

US07045677B2 Fusion proteins incorporating lysozyme 有权
公开(公告)号：US07045677B2
公开(公告)日：2006-05-16
申请号：US10024597
申请日：2001-12-21
申请人： Ian Robert Cottingham , Graham Edward McCreath
发明人： Ian Robert Cottingham , Graham Edward McCreath
IPC分类号： A01K67/27
CPC分类号： C12N15/8509 , A01K67/0278 , A01K2207/15 , A01K2217/00 , A01K2217/05 , A01K2227/103 , A01K2227/105 , A01K2227/107 , A01K2267/01 , C07K14/585 , C07K14/605 , C07K2319/00 , C07K2319/50 , C07K2319/75 , C12N9/2462 , C12N15/62
摘要： 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.

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