DNA sequences that encode a natural resistance to infection with intracellular parasites
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.
Claims31
An isolated nucleic acid molecule comprising a polynucleotide sequence encoding Nramp, wherein Nramp is a transmembrane protein having at least 10 transmembrane domains and a binding-protein-dependent transport system inner membrane component signature of bacteria, which participates in substrate translocation across a membrane, and wherein said Nramp confers resistance to infection to unrelated intracellular parasites, said polynucleotide sequence selected from the group consisting of:
- a) SEQ ID NO:1;
- b) SEQ ID NO:24;
- c) SEQ ID NO:26;
- d) SEQ ID NO:29;
- e) SEQ ID NO:31;
- and
- f) a nucleotide sequence encoding an amino acid sequence which is at least 93% homologous to an amino acid sequence encoded by any of the polynucleotide sequences in (a) to (e).
An isolated nucleic acid molecule comprising a polynucleotide sequence encoding Nramp, wherein Nramp is a transmembrane protein having at least 10 transmembrane domains and a binding-protein-dependent transport system inner membrane component signature of bacteria, which participates in substrate translocation across a membrane, and wherein said Nramp confers resistance to infection to unrelated intracellular parasites, said polynucleotide sequence selected from the group consisting of:
- a) a polynucleotide sequence encoding SEQ ID NO:2;
- b) a polynucleotide sequence encoding SEQ ID NO:25;
- c) a polynucleotide sequence encoding SEQ ID NO:27;
- d) a polynucleotide sequence encoding SEQ ID NO:28;
- e) a polynucleotide sequence encoding SEQ ID NO:30;
- f) a polynucleotide sequence encoding SEQ ID NO:32;
- and
- g) a polynucleotide sequence encoding an amino acid sequence which is at least 93% homologous to an amino acid sequence encoded by any of the polynucleotide sequences in (a) to (f).
An isolated nucleic acid molecule consisting of a polynucleotide sequence selected from the group consisting of:
- a) SEQ ID NO:1;
- b) SEQ ID NO:24;
- c) SEQ ID NO:26;
- d) SEQ ID NO:29;
- e) SEQ ID NO:31;
- and
- f) a nucleotide sequence fully complementary to any of the polynucleotide sequences in (a) to (e).
An isolated nucleic acid molecule consisting of a polynucleotide sequence selected from the group consisting of:
- a) a polynucleotide sequence encoding SEQ ID NO:2;
- b) a polynucleotide sequence encoding SEQ ID NO:25;
- c) a polynucleotide sequence encoding SEQ ID NO:27;
- d) a polynucleotide sequence encoding SEQ ID NO:28;
- e) a polynucleotide sequence encoding SEQ ID NO:30;
- f) a polynucleotide sequence encoding SEQ ID NO:32;
- and
- g) a nucleotide sequence fully complementary to any of the polynucleotide sequences in (a) to (f).
An isolated nucleic acid molecule encoding a mutant SEQ ID NO:2, wherein said mutant comprises a glycine at position 105.
Dependencies are inferred from the claim text.