Methods of screening for compounds that regulate the level of Nramp
AssigneeMcGill University
InventorsPhilippe Gros, Emil Skamene, Danielle Malo, Silvia Vidal
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Abstract
The present invention relates to mouse and human cDNAs for a gene family designated Nramp (natural resistance-associated macrophage protein), involved in macrophage function and responsible for the natural resistance to infection with intracellular parasites, and to the isolation of Nramp sequences from other animal sources. The nucleotide sequences of the mouse and human cDNAs are disclosed, as are the amino sequences of the encoded products. The cDNAs can be expressed in expression constructs. These expression constructs and the proteins produced therefrom can be used for a variety of purposes including diagnostic and therapeutic methods.
Claims21
A method of screening for compounds that regulate the level of Nramp, wherein Nramp is a transmembrane protein which participates in substrate translocation across a cellular membrane, and wherein Nramp confers resistance to infection to unrelated intracellular parasites,
- wherein said method comprises expressing a nucleic acid sequence encoding Nramp in a eukaryotic or prokaryotic host cell, and monitoring changes in Nramp level upon treatment with said compound, wherein said Nramp comprises an amino acid sequence selected from the group consisting of:
- a) SEQ ID NO:2;
- b) SEQ ID NO:4;
- c) SEQ ID NO:6;
- d) SEQ ID NO:25;
- e) SEQ ID NO:27;
- f) SEQ ID NO:28;
- g) SEQ ID NO:30;
- h) SEQ ID NO:32;
- i) SEQ ID NO:33;
- and
- j) an amino acid sequence which is at least 93% homologous to one of the amino acid sequences in a) to i);
- and wherein a compound that regulates Nramp level is identified when said Nramp level is measurably different in the presence of said compound as compared to in the absence thereof.
A method of screening for compounds that regulate the level of Nramp, wherein Nramp is a transmembrane protein which participates in substrate translocation across a cellular membrane, and wherein Nramp confers resistance to infection to unrelated intracellular parasites,
- wherein said method comprises expressing a polynucleotide sequence encoding Nramp in a eukaryotic or prokaryotic host cell, and monitoring changes in Nramp level upon treatment with said compound,
- wherein said polynucleotide comprises a nucleotide sequence selected from the group consisting of:
- a) SEQ ID NO:1;
- b) SEQ ID NO:3;
- c) SEQ ID NO:5;
- d) SEQ ID NO:24;
- e) SEQ ID NO:26;
- f) SEQ ID NO:29;
- g) SEQ ID NO:31;
- h) a polynucleotide sequence which hybridizes under high stringency conditions to any of the polynucleotide sequences in (a) to (h);
- wherein a compound that regulates Nramp level is identified when said Nramp level is measurably different in the presence of said compound as compared to in the absence thereof.
A method of screening for compounds that regulate the level of Nramp, wherein Nramp is a transmembrane protein which participates in substrate translocation across a cellular membrane, and wherein Nramp confers resistance to infection to unrelated intracellular parasites,
- wherein said method comprises expressing a nucleic acid sequence comprising a polynucleotide sequence encoding a Nramp amino acid sequence in a eukaryotic or prokaryotic host cell, and monitoring changes in Nramp function or level upon treatment with said compound, wherein said Nramp amino acid sequence is selected from the group consisting of:
- a) SEQ ID NO:2;
- b) SEQ ID NO:4;
- c) SEQ ID NO:6;
- d) SEQ ID NO:25;
- e) SEQ ID NO:27;
- f) SEQ ID NO:28;
- g) SEQ ID NO:30;
- h) SEQ ID NO:32;
- i) SEQ ID NO:33;
- and
- j) an amino acid sequence which is at least 93% homologous to one of the amino acid sequences in a) to i);
- wherein a compound that regulates Nramp level is identified when said Nramp level is measurably different in the presence of said compound as compared to in the absence thereof.
A method of screening for compounds that regulate the level of Nramp, wherein Nramp is a transmembrane protein which participates in substrate translocation across a cellular membrane,
- wherein said method comprises expressing a nucleic acid sequence encoding Nramp in a eukaryotic or prokaryotic host cell, and monitoring changes in Nramp level upon treatment with the compound, wherein Nramp comprises an amino acid sequence selected from the group consisting of:
- a) SEQ ID NO:2;
- b) SEQ ID NO:4;
- c) SEQ ID NO:6;
- d) SEQ ID NO:25;
- e) SEQ ID NO:27;
- f) SEQ ID NO:28;
- g) SEQ ID NO:30;
- h) SEQ ID NO:32;
- and
- i) SEQ ID NO:33;
- and wherein a compound that regulates Nramp level is identified when the Nramp level is measurably different in the presence of the compound as compared to in the absence thereof.
A method of screening for compounds that regulate the level of Nramp, wherein Nramp is a transmembrane protein which participates in substrate translocation across a cellular membrane,
- wherein said method comprises expressing a polynucleotide sequence encoding Nramp in a eukaryotic or prokaryotic host cell, and monitoring changes in Nramp level upon treatment with said compound,
- wherein said polynucleotide comprises a nucleotide sequence selected from the group consisting of:
- a) SEQ ID NO:1;
- b) SEQ ID NO:3;
- c) SEQ ID NO:5;
- d) SEQ ID NO:24;
- e) SEQ ID NO:26;
- f) SEQ ID NO:29;
- and
- g) SEQ ID NO:31;
- wherein a compound that regulates Nramp level is identified when the Nramp level is measurably different in the presence of said compound as compared to in the absence thereof.
A method of screening for compounds that regulate the level of Nramp, wherein Nramp is a transmembrane protein which participates in substrate translocation across a cellular membrane,
- wherein said method comprises expressing a nucleic acid sequence comprising a polynucleotide sequence encoding a Nramp amino acid sequence in a eukaryotic or prokaryotic host cell, and monitoring changes in Nramp function or level upon treatment with the compound, wherein the Nramp amino acid sequence is selected from the group consisting of:
- a) SEQ ID NO:2;
- b) SEQ ID NO:4;
- c) SEQ ID NO:6;
- d) SEQ ID NO:25;
- e) SEQ ID NO:27;
- f) SEQ ID NO:28;
- g) SEQ ID NO:30;
- h) SEQ ID NO:32;
- and
- i) SEQ ID NO:33;
- wherein a compound that regulates Nramp level is identified when said Nramp level is measurably different in the presence of the compound as compared to in the absence thereof.
A method of screening for compounds that regulate the level of Nramp, wherein Nramp is a transmembrane protein which participates in substrate translocation across a cellular membrane,
- wherein said method comprises expressing a nucleic acid sequence comprising a polynucleotide sequence encoding a Nramp amino acid sequence in a eukaryotic or prokaryotic host cell, and monitoring changes in Nramp function or level upon treatment with said compound, wherein said Nramp amino acid sequence is selected from the group consisting of:
- a) SEQ ID NO:2;
- b) SEQ ID NO:4;
- c) SEQ ID NO:6;
- d) SEQ ID NO:25;
- e) SEQ ID NO:27;
- f) SEQ ID NO:28;
- g) SEQ ID NO:30;
- h) SEQ ID NO:32;
- and
- i) SEQ ID NO:33;
- wherein a compound that regulates Nramp level is identified when the Nramp level is measurably different in the presence of said compound as compared to in the absence thereof.
Dependencies are inferred from the claim text.