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Novel 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt molecules and uses therefor

a technology of fbh58295fl and molecule, which is applied in the field of new 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, etc., can solve problems such as uncontrolled growth

Inactive Publication Date: 2006-01-12
MILLENNIUM PHARMA INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The present invention is based on the discovery of new members of the MTP-1 family of transporter molecules, which are related to the ABC transporter molecules involved in cellular transmembrane lipid transport. These MTP-1 molecules are found to be preferentially expressed in myelo-lymphatic tissue and are believed to play a role in hematopoietic and immunological diseases, as well as lipid metabolism disorders such as atherosclerosis. The invention provides isolated nucleic acid molecules and nucleic acid fragments that can detect and / or encode MTP-1 molecules, as well as methods for producing MTP-1 proteins. The technical effects of the invention include the identification of new MTP-1 molecules and their use in the diagnosis and treatment of related diseases.

Problems solved by technology

When Fhit is mutated cells cannot sense ApnA stress signals, which can result in uncontrolled growth.

Method used

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  • Novel 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt molecules and uses therefor
  • Novel 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt molecules and uses therefor
  • Novel 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt molecules and uses therefor

Examples

Experimental program
Comparison scheme
Effect test

example 1

Identification and Characterization of Human MTP-1 cDNA

[1018] In this example, the identification and characterization of the gene encoding human MTP-1 (clone Fbh38594) is described.

Isolation of the MTP-1 cDNA

[1019] The invention is based, at least in part, on the discovery of a human genes encoding a novel protein, referred to herein as MTP-1. The entire sequence of human clones Fbh38594, was determined and found to contain an open reading frame termed human “MTP-1”. The MTP-1 protein sequence set forth in SEQ ID NO:2 comprises about 2144 amino acids. The coding region (open reading frame) of SEQ ID NO:1, is set forth as SEQ ID NO:3.

Analysis of the Human MTP-1 Molecule

[1020] An analysis of the possible cellular localization of the MTP-1 protein based on its amino acid sequence was performed using the methods and algorithms described in Nakai and Kanehisa (1992) Genomics 14:897-911, and at http: / / psort.nibb.ac.jp. The results of the analysis show that human MTP-1 (SEQ ID NO:2...

example 2

Expression of Recombinant MTP-1, OAT, HST-1, TP-2, PLTR-1, TFM-2, TFM-3, 67118, 67067, 62092, HAAT, HST-4 and HST-5 Polypeptides in Bacterial Cells

[1026] In this example, In this example, human MTP-1, human OAT, human HST-1, human TP-2, human PLTR-1, human TFM-2, human TFM-3, human 67118, human 67067, human 62092, human HAAT, human HST-4 and / or human HST-5 is expressed as a recombinant glutathione-S-transferase (GST) fusion polypeptide in E. coli and the fusion polypeptide is isolated and characterized. Specifically, MTP-1, OAT, HST-1, TP-2, PLTR-1, TFM-2, TFM-3, 67118, 67067, 62092, HAAT, HST-4 and / or HST-5 is fused to GST and this fusion polypeptide is expressed in E. coli, e.g., strain PEB199. Expression of the GST- MTP-1, GST-OAT, GST-HST-1, GST-TP-2, GST-PLTR-1, GST-TFM-2, GST-TFM-3, GST-67118, GST-67067, GST-62092, GST-HAAT, GST-HST-4, or GST-HST-5 fusion protein in PEB199 is induced with IPTG. The recombinant fusion polypeptide is purified from crude bacterial lysates of the...

example 3

Expression of Recombinant MTP-1, OAT, HST-1, TP-2, PLTR-1, TFM-2, TFM-3, 67118, 67067, 62092, HAAT, HST-4 and HST-5 Protein in Cos Cells

[1027] To express the MTP-1, OAT, HST-1, TP-2, PLTR-1, TFM-2, TFM-3, 67118, 67067, 62092, HAAT, HST-4, or HST-5 gene in COS cells, the pcDNA / Amp vector by Invitrogen Corporation (San Diego, Calif.) is used. This vector contains an SV40 origin of replication, an ampicillin resistance gene, an E. coli replication origin, a CMV promoter followed by a polylinker region, and an SV40 intron and polyadenylation site. A DNA fragment encoding the entire MTP-1, OAT, HST-1, TP-2, PLTR-1, TFM-2, TFM-3, 67118, 67067, 62092, HAAT, HST-4, or HST-5 protein and an HA tag (Wilson et al. (1984) Cell 37:767) or a FLAG tag fused in-frame to its 3′ end of the fragment is cloned into the polylinker region of the vector, thereby placing the expression of the recombinant protein under the control of the CMV promoter.

[1028] To construct the plasmid, the MTP-1, OAT, HST-1, ...

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Abstract

The invention provides isolated nucleic acids molecules, designated 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt nucleic acid molecules, which encode transporter molecules, including sugar transporters, organic anion transporters, amino acid transporters, and phospholipid transporters. The invention also provides antisense nucleic acid molecules, recombinant expression vectors containing 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt nucleic acid molecules, host cells into which the expression vectors have been introduced, and non-human transgenic animals in which a 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt gene has been introduced or disrupted. The invention still further provides isolated 38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt polypeptides, fusion polypeptides, antigenic peptides and anti-38594, 57312, 53659, 57250, 63760, 49938, 32146, 57259, 67118, 67067, 62092, FBH58295FL, 57255, and 57255alt antibodies. Diagnostic and therapeutic methods utilizing compositions of the invention are also provided.

Description

RELATED APPLICATIONS [0001] This application is a divisional of U.S. patent application Ser. No. 10 / 154,419, filed May 22, 2002 (pending), published as U.S. patent application Publication No. 2003-0143675 A1 on Jul. 31, 2003, which is: [0002] a continuation-in-part of U.S. patent application Ser. No. 09 / 858,194, filed May 14, 2001, published as U.S. patent application Publication No. 2002-0061590 A1 (abandoned), which claims the benefit of U.S. Provisional Application Ser. No. 60 / 204,211, filed May 12, 2000; [0003] also a continuation-in-part of U.S. patent application Ser. No. 09 / 895,811, filed Jun. 29, 2001 (abandoned), which claims the benefit of U.S. Provisional Application Ser. No. 60 / 215,376, filed Jun. 29, 2000; [0004] also a continuation-in-part of U.S. patent application Ser. No. 09 / 919,781, filed Jul. 31, 2001, published as U.S. patent application Publication No. 2002-0123094 A1 (abandoned), which claims the benefit of U.S. Provisional Application Ser. No. 60 / 221,769, file...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C12Q1/68C07H21/04C12P21/06C07K14/705A61K38/00A61K48/00C07K14/47C12N9/14C12N9/16G01N33/50G01N33/68
CPCA01K2217/05G01N2500/20A61K38/00A61K48/00C07K14/47C07K14/4702C07K14/705C07K2319/00C12N9/14C12N9/16C12N2310/3181C12N2310/351G01N2500/02G01N2500/04G01N2500/10A01K2217/075
Inventor CURTIS, RORY A.J.GLUCKSMANN, MARIA ALEXANDRAMEYERS, RACHEL E.
Owner MILLENNIUM PHARMA INC
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