公开(公告)号：US20060110792A1

公开(公告)日：2006-05-25

申请号：US11178538

申请日：2005-07-12

Applicant: Mark Pausch ,  Laura Price

Inventor： Mark Pausch ,  Laura Price

IPC: C07K14/705 ,  C07H21/04 ,  C12P21/06

CPC classification number: C07K14/705 ,  C07K14/43545 ,  C07K14/43581 ,  C07K14/47 ,  C12Q1/025 ,  G01N33/6872

Abstract: This invention relates generally to a new family of potassium channels. More particularly, the present invention relates to the cloning and characterization of a family of distinct trans-membrane potassium ion channels, characterization of such channels, newly identified polynucleotide sequences, polypeptides encoded by such sequences, expression vectors capable of heterologous expression of such polynucleotide sequences, transformed host cells containing the expression vectors, and assay methods and kits therefor for determining the expression of heterologous nucleotide sequences encoding all or a portion of said potassium channels in host cells, chromosome mapping, diagnostic methodologies and kits therefore. Genes encoding potassium channels representative of this family were cloned from Drosophila melanogaster, Caenorhabditis elegans, human and mouse ESTs, and human brain, heart and kidney cDNA libraries. More particularly, the invention arises in part from the determination that the DNA sequences of these genes encode a structurally distinct potassium channel whose molecular architecture is characterized by four membrane spanning domains and two putative pore forming domains.

Abstract translation: 本发明一般涉及新的钾通道家族。 更具体地说，本发明涉及不同跨膜钾离子通道家族的克隆和表征，这些通道的表征，新鉴定的多核苷酸序列，由这些序列编码的多肽，能够异源表达这种多核苷酸序列的表达载体 ，含有表达载体的转化的宿主细胞，以及用于确定宿主细胞中编码所有或部分所述钾通道的异源核苷酸序列的表达的测定方法和试剂盒，因此染色体图谱，诊断方法和试剂盒。 从黑腹果蝇，秀丽隐杆线虫，人和小鼠EST以及人脑，心脏和肾脏cDNA文库克隆了代表该家族的钾通道的基因。 更具体地说，本发明的部分原因在于确定这些基因的DNA序列编码结构不同的钾通道，其分子结构的特征在于四个膜跨越结构域和两个推定的成孔结构域。

公开(公告)号：US06958320B2

公开(公告)日：2005-10-25

申请号：US10811199

申请日：2004-03-26

Applicant: Iva Greenwald ,  Diane Levitan

Inventor： Iva Greenwald ,  Diane Levitan

IPC: A01K67/027 ,  A01K67/033 ,  A61K31/00 ,  A61K31/70 ,  A61K31/7088 ,  A61K38/00 ,  A61K48/00 ,  A61P25/28 ,  C07H21/02 ,  C07K14/435 ,  C07K16/18 ,  C12N1/21 ,  C12N5/10 ,  C12N15/00 ,  C12N15/09 ,  C12N15/12 ,  C12N15/84 ,  C12P21/02 ,  C12R1/91

CPC classification number: C07K14/43545 ,  A01K2217/05 ,  A61K38/00

Abstract: This invention provides an isolated nucleic acid molecule encoding a SEL-12. This invention further provides an isolated nucleic acid molecule which encodes a mutated SEL-12. This invention also provides an isolated nucleic acid molecule which encodes a mutated SEL-12, wherein the mutated SEL-12 contains at least one of the following: position 115 is a leucine, position 132 is an arginine, position 215 is a glutamic acid, position 229 is a valine, position 254 is a valine, position 255 is a valine, position 371 is a valine, position 387 is a tyrosine, position 104 is an isoleucine or position 204 is a valine. This invention further provides different uses of these nucleic acid molecules. This invention also provides different sel-12 mutants and transgenic animals which carry wild-type or mutated sel-12.

Abstract translation: 本发明提供了编码SEL-12的分离的核酸分子。 本发明还提供了编码突变的SEL-12的分离的核酸分子。 本发明还提供了编码突变的SEL-12的分离的核酸分子，其中突变的SEL-12含有以下至少一种：位置115是亮氨酸，位置132是精氨酸，位置215是谷氨酸， 位置229是缬氨酸，位置254是缬氨酸，位置255是缬氨酸，位置371是缬氨酸，位置387是酪氨酸，位置104是异亮氨酸或位置204是缬氨酸。 本发明进一步提供了这些核酸分子的不同用途。 本发明还提供携带野生型或突变型sel-12的不同的sel-12突变体和转基因动物。

公开(公告)号：US20050032165A1

公开(公告)日：2005-02-10

申请号：US10870492

申请日：2004-06-18

Applicant: Mark Pausch

Inventor： Mark Pausch

IPC: C07K14/435 ,  C07K14/47 ,  C07K14/705 ,  C12N15/82 ,  C12Q1/02 ,  G01N33/68 ,  C12P21/02 ,  C07H21/04

CPC classification number: G01N33/6872 ,  C07K14/43545 ,  C07K14/43581 ,  C07K14/47 ,  C07K14/705 ,  C12N15/8261 ,  C12Q1/025 ,  Y02A40/146

Abstract: This invention relates generally to a new family of potassium channels, whose molecular architecture is characterized by four membrane spanning domains and two putative pore forming domains. More particularly, the present invention relates to the cloning and characterization of mutants of this family of distinct trans-membrane potassium ion channels which confer improved inward potassium flux under acidic conditions, characterization of such channels, newly identified polynucleotide sequences, polypeptides encoded by such sequences, expression vectors capable of heterologous expression of such polynucleotide sequences, transformed host cells containing the expression vectors, and assay methods and kits therefor for determining the expression of heterologous nucleotide sequences encoding all or a portion of said potassium channels in host cells, chromosome mapping, diagnostic methodologies and kits therefore.

Abstract translation: 本发明一般涉及新的钾通道家族，其分子结构的特征在于四个膜跨越结构域和两个推定的成孔结构域。 更具体地，本发明涉及克隆和表征这种不同的跨膜钾离子通道家族的突变体，其在酸性条件下赋予改善的向内钾通量，表征这些通道，新鉴定的多核苷酸序列，由这些序列编码的多肽 能够异源表达这些多核苷酸序列的表达载体，含有表达载体的转化宿主细胞，以及用于确定编码宿主细胞中所有或部分所述钾通道的异源核苷酸序列的表达的测定方法和试剂盒，染色体测定， 因此诊断方法和工具包。

公开(公告)号：US20040265839A1

公开(公告)日：2004-12-30

申请号：US10645746

申请日：2003-08-20

Applicant: UNIVERSITY OF MASSACHUSETTS MEDICAL

Inventor： Craig C. Mello ,  Andrew Fire ,  Hiroaki Tabara ,  Alla Grishok

IPC: C12Q001/68 ,  C07H021/04 ,  C12N009/22 ,  C12N015/85

CPC classification number: C12N15/67 ,  C07K14/43545

Abstract: Genes involved in double-stranded RNA interference (RNAi pathway genes) are identified and used to investigate the RNAi pathway. The genes and their products are also useful for modulating RNAi pathway activity.

Abstract translation: 鉴定涉及双链RNA干扰基因（RNAi途径基因）并用于研究RNAi途径。 基因及其产物也可用于调节RNAi通路活性。

公开(公告)号：US06723557B1

公开(公告)日：2004-04-20

申请号：US09479467

申请日：2000-01-06

Applicant: Paul W. Sternberg ,  Maureen M. Barr

Inventor： Paul W. Sternberg ,  Maureen M. Barr

IPC: C12N1500

CPC classification number: A01K67/0333 ,  A01K2217/05 ,  A61K48/00 ,  C07K14/43545

Abstract: Nematodes, such as Caenorhabditis elegans, that express mutant and wild-type orthologs of human genes involved in polycystic kidney diseases (PKDs), are used to study the functions of the proteins encoded by the genes, to screen for other genes involved in the diseases, to identify mutations involved in the diseases, and to screen for drugs that affect PKD. Behaviors controlled by the action of the genes or gene products are identified and used in the assays. Hence an animal model is provided that permits study of the etiology of polycystic kidney disease and provides a tool to identify the genes involved in the disease pathway, and to identify compounds that may be used to treat or alter the disease progression, lessen its severity or ameliorate symptoms. The nematode genes that encode protein products, mutants of the genes, vectors contain the genes and mutant genes and nematode strains that contain the vectors are also provided.

Abstract translation: 用于表达参与多囊肾病（PKD）的人类基因的突变体和野生型直向同源物的秀丽隐杆线虫等线虫被用于研究由该基因编码的蛋白质的功能，以筛选涉及该疾病的其它基因 ，以鉴定涉及疾病的突变，并筛选影响PKD的药物。 通过基因或基因产物的作用控制的行为被鉴定并用于测定。 因此，提供了允许研究多囊肾病的病因的动物模型，并且提供了鉴定参与疾病途径的基因的工具，并且鉴定可用于治疗或改变疾病进展的化合物，减轻其严重性或 改善症状。 编码蛋白质产物的线虫基因，基因的突变体，载体含有含有载体的基因和突变基因和线虫菌株。

公开(公告)号：US20030165806A1

公开(公告)日：2003-09-04

申请号：US08816011

申请日：1997-03-11

Inventor： MARK H. PAUSCH

IPC: C12Q001/00 ,  C07H021/04 ,  C12N001/18 ,  C07K014/47 ,  C12P021/02 ,  C12N005/06

CPC classification number: C07K14/705 ,  C07K14/43545 ,  C07K14/43581 ,  C07K14/47 ,  C12Q1/025 ,  G01N33/6872

Abstract: This invention relates generally to a new family of potassium channels. More particularly, the present invention relates to the cloning and characterization of a family of distinct trans-membrane potassium ion channels, characterization of such channels, newly identified polynucleotide sequences, polypeptides encoded by such sequences, expression vectors capable of heterologous expression of such polynucleotide sequences, transformed host cells containing the expression vectors, and assay methods and kits therefor for determining the expression of heterologous nucleotide sequences encoding all or a portion of said potassium channels in host cells, chromosome mapping, diagnostic methodologies and kits therefore. Genes encoding potassium channels representative of this family were cloned from Drosophila melanogaster, Caenorhabditis elegans, human and mouse ESTs, and human brain, heart and kidney cDNA libraries. More particularly, the invention arises in part from the determination that the DNA sequences of these genes encode a structurally distinct potassium channel whose molecular architecture is characterized by four membrane spanning domains and two putative pore forming domains.

Abstract translation: 本发明一般涉及新的钾通道家族。 更具体地说，本发明涉及不同跨膜钾离子通道家族的克隆和表征，这些通道的表征，新鉴定的多核苷酸序列，由这些序列编码的多肽，能够异源表达这种多核苷酸序列的表达载体 ，含有表达载体的转化的宿主细胞，以及用于确定宿主细胞中编码所有或部分所述钾通道的异源核苷酸序列的表达的测定方法和试剂盒，因此染色体图谱，诊断方法和试剂盒。 从黑腹果蝇，秀丽隐杆线虫，人和小鼠EST以及人脑，心脏和肾脏cDNA文库克隆了代表该家族的钾通道的基因。 更具体地说，本发明的部分原因在于确定这些基因的DNA序列编码结构不同的钾通道，其分子结构的特征在于四个膜跨越结构域和两个推定的成孔结构域。

公开(公告)号：US20030162291A1

公开(公告)日：2003-08-28

申请号：US10312187

申请日：2003-04-09

Inventor： Seigfried Hekimi ,  Claire Benard ,  Brenton McCright ,  Bernard Lakowski ,  Dong Han ,  Jean-Claude Labbe

IPC: A61K048/00 ,  C12N005/02 ,  C07H021/04

CPC classification number: C07K14/43545 ,  C07K14/47

Abstract: The present invention relates to a clk-2 gene which has a function at the level of cellular physiology involved in developmental rate, telomere length and longevity, wherein clk-2 mutations cause a longer life, an altered cellular metabolism and an altered telomere length relative to the wild type, wherein clk-2 overexpression leads to telomere shortening. The present invention also relates to clk-2 co-expressed gene which comprises a cex-7 gene having the nucleotide sequence set forth in FIG. 33 which codes for a CEX-7 protein having the amino acid sequence set forth in FIG. 34 wherein said gene is located in the clk-2 operon and said cex-7 gene is transcriptionally co-expressed with clk-2 gene present in said operon. The present invention also relates to a coq-4 gene which has a function at the level of cellular physiology involved in the regulation of developmental rate and longevity, wherein coq-4 mutations cause altered cellular metabolism and physiological relative to the wild type, wherein coq-4 gene has the identifying characteristics of nucleotide sequence set forth in FIG. 36.

Abstract translation: 本发明涉及具有涉及发育率，端粒长度和寿命的细胞生理学水平的功能的clk-2基因，其中clk-2突变引起更长的寿命，改变的细胞代谢和改变的端粒长度相对 到野生型，其中clk-2过表达导致端粒缩短。 本发明还涉及包含具有图1所示的核苷酸序列的cex-7基因的clk-2共表达基因。 33编码具有图1所示氨基酸序列的CEX-7蛋白。 34，其中所述基因位于clk-2操纵子中，并且所述cex-7基因与存在于所述操纵子中的clk-2基因转录共表达。 本发明还涉及一种coq-4基因，其具有参与调节发育率和寿命的细胞生理学水平的功能，其中coq-4突变引起相对于野生型改变的细胞代谢和生理学，其中coq -4基因具有图1所示的核苷酸序列的鉴定特征。 36。

公开(公告)号：US20030131378A1

公开(公告)日：2003-07-10

申请号：US10344440

申请日：2003-02-10

Inventor： Raffi V. Aroian

IPC: A01H001/00 ,  C12N015/82

CPC classification number: A01N63/02 ,  A01N37/46 ,  C07K14/43545 ,  C12N9/1051 ,  C12N15/8285 ,  C12N15/8286 ,  Y02A40/162 ,  Y02A40/164

Abstract: Two genes involved in the resistance of insects to Bacillus thruingiensis toxins have been cloned providing an understanding of mechanisms of resistance to the toxins. Such an understanding allows for rational methods to modify or combine toxins to prevent or overcome Bt toxin resistance to improve crop protection.

Abstract translation: 已经克隆了涉及昆虫对芽孢杆菌毒素的抗性的两个基因，提供了对毒素抗性机制的理解。 这样的理解允许合理的方法来修饰或组合毒素以预防或克服Bt毒素抗性来改善作物保护。

公开(公告)号：US20030108987A1

公开(公告)日：2003-06-12

申请号：US10153398

申请日：2002-05-21

Applicant: The Regents of the University of California

Inventor： Joel H. Rothman ,  Erin Newman-Smith ,  Gina Broitman-Maduro

IPC: C07K014/72 ,  C12P021/02 ,  C12N005/06 ,  C07H021/04

CPC classification number: G01N33/5023 ,  A01K67/0336 ,  A01K2217/05 ,  A01K2227/703 ,  A01K2267/03 ,  C07K14/43545 ,  C07K14/721 ,  C07K2319/41 ,  C12N2830/002 ,  G01N33/5008 ,  G01N33/502 ,  G01N33/6875 ,  G01N33/743 ,  G01N2333/4353 ,  G01N2333/70567 ,  G01N2500/10

Abstract: This invention pertains to the discovery that DPR-1 encodes a putative nuclear hormone receptor (NHR) that, based on gene reporter studies, is expressed in the endoderm throughout the life of the worm. NHR family members are transcriptional regulators that are activated when bound to their small lipophilic ligands such as steroids. While some NHRs are localized to the nucleus, others are cytoplasmic in the absence of ligand and translocate to the nucleus upon ligand binding. Once in the nucleus, they bind target sequences and regulate gene expression.

Abstract translation: 本发明涉及DPR-1编码推定的核激素受体（NHR）的发现，其基于基因报告基因研究，在蠕虫的整个生命周期内在内胚层中表达。 NHR家族成员是转录调节因子，当与其小的亲脂性配体如类固醇结合时被激活。 虽然一些NHR定位于细胞核，其他的则在配体不存在的情况下是细胞质的，并在配体结合时转移到细胞核。 一旦在细胞核中，它们结合靶序列并调节基因表达。

公开(公告)号：US20020007496A1

公开(公告)日：2002-01-17

申请号：US09860113

申请日：2001-05-16

Inventor： Joel H. Rothman ,  William Brent Derry

IPC: A01K067/033 ,  C07H021/04

CPC classification number: C07K14/43545

Abstract: The present invention identifies a p53 homolog gene, cep-1, and mutations thereof in the nematode C. elegans which allows for the application of molecular genetic methods to identify new components of the p53 pathway as well as genes that act in parallel to the p53 pathway. cep-1 mutants show elevated physiological germ cell death during normal development. The present invention also provides a simple system with which to perform high-throughput screens for pharmacological agents that suppress the effects of eliminating the cep-1 gene or that enhance its effectiveness when in a mutant state. This strategy should identify agents that selectively kill p53-deficient cells that are resistant to traditional chemotherapeutic regimens and thus block the formation of human tumors that arise when p53 function is compromised.

Abstract translation: 本发明鉴定了线虫C.线虫中的p53同源基因cep-1及其突变，其允许应用分子遗传学方法来鉴定p53途径的新成分以及与p53平行起作用的基因 途径。 cep-1突变体在正常发育过程中显示生理生殖细胞死亡升高。 本发明还提供了一种简单的系统，用于对抑制cep-1基因的消除作用的药理学试剂进行高通量筛选，或者在突变状态下提高其效力。 该策略应该确定选择性地杀死对传统化学治疗方案有抗性的p53缺陷型细胞的药剂，从而阻断当p53功能受损时产生的人类肿瘤的形成。