Isolation, characterization, and use of a novel teleost potassium channel
OwnerUlrike Langheinrichinventor
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Abstract
The present invention provides nucleic acid and polypeptide sequences associated with teleost ERG genes, which encode ERG family potassium channels. The invention further provides teleost models for cardiac function and methods of screening for cardio-active agents using mutant teleost larvae having reduced teleost ERG activity.
Claims25
An isolated nucleic acid molecule comprising a polynucleotide sequence that encodes or is complementary to a sequence that encodes a teleost ERG polypeptide.
An antisense oligomer capable of inactivating a ZERG gene comprising a nucleotide sequence complementary to at least 10 contiguous nucleotides within nucleotides 1-150 of SEQ ID NO:1.
A genetically modified teleost comprising an endogenous teleost ERG gene wherein expression of the teleost ERG gene has been specifically disrupted by admininstration of a PMO comprising a nucleotide sequence complementary to a fragment of the teleost ERG gene.
A method of identifying a cardio-active agent comprising the steps of:
- a) providing mutant teleost larvae having reduced teleost ERG activity;
- b) contacting the teleost larvae with a candidate agent;
- c) detecting an agent-biased cardiac phenotype in the mutant teleost larvae,
- wherein detection of an agent-biased cardiac phenotype indicates that the candidate agent is a cardio-active agent.
A chimeric ZERG gene encoding a chimeric polypeptide have an amino acid sequence derived from the sequence presented as SEQ ID NO:2, wherein the chimeric polypeptide comprises at least one sequence replacement selected from the group consisting of:
- (i) replacing amino acid 376 of SEQ ID NO:2 with amino acid 413 of SEQ ID NO:5,
- (ii) replacing amino acids 388-413 of SEQ ID NO:2 with amino acids 425-451 of SEQ ID NO:5,
- (iii) replacing amino acids 414-434 of SEQ ID NO:2 with amino acids 452-472 of SEQ ID NO:5,
- (iv) replacing amino acids 435-458 of SEQ ID NO:2 with amino acids 437-496 of SEQ ID NO:5,
- (v) replacing amino acid 476 of SEQ ID NO:2 with amino acid 514 of SEQ ID NO:5,
- (vi) replacing amino acids 540-575 of SEQ ID NO:2 with amino acids 573-603 of SEQ ID NO:5,
- (vii) replacing amino acid 608 of SEQ ID NO:2 with amino acid 636 of SEQ ID NO:5.
Dependencies are inferred from the claim text.