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AssigneeKeio University
InventorsHideyuki Okano, Hirotaka James Okano, Chikako Miyauchi
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To generate an animal model exhibiting symptoms similar to those of human amyotrophic lateral sclerosis and/or human frontotemporal lobar degeneration. An animal model exhibiting symptoms similar to those of human amyotrophic lateral sclerosis and/or human frontotemporal lobar degeneration can be produced by means of generating a mutation in a vertebrate so that expression of a mutant protein with a substitution of tyrosine for alanine at a position corresponding to position 382 of SEQ ID NO. 1 or a mutant protein with a substitution of cysteine for glycine at a position corresponding to position 348 of SEQ ID NO. 1 is regulated by an endogenous TDP-43 gene promoter in at least one allele of an endogenous TDP-43 gene of the vertebrate.
A non-human vertebrate wherein expression of a mutant protein with a substitution of tyrosine for alanine at a position corresponding to position 382 of SEQ ID NO. 1 or a mutant protein with a substitution of cysteine for glycine at a position corresponding to position 348 of SEQ ID NO. 1 is regulated by an endogenous TDP-43 gene promoter in at least one allele of an endogenous TDP-43 gene.
A method of generating an animal model of amyotrophic lateral sclerosis, comprising the step of generating a mutation in a non-human vertebrate so that expression of a mutant protein with a substitution of tyrosine for alanine at a position corresponding to position 382 of SEQ ID NO. 1 or a mutant protein with a substitution of cysteine for glycine at a position corresponding to position 348 of SEQ ID NO. 1 is regulated by an endogenous TDP-43 gene promoter in at least one allele of an endogenous TDP-43 gene of the vertebrate.
The method of producing an animal model of frontotemporal lobar degeneration, comprising the step of generating a mutation in a non-human vertebrate so that expression of a mutant protein with a substitution of tyrosine for alanine at a position corresponding to position 382 of SEQ ID NO. 1 or a mutant protein with a substitution of cysteine for glycine at a position corresponding to position 348 of SEQ ID NO. 1 is regulated by an endogenous TDP-43 gene promoter in at least one allele of the endogenous TDP-43 gene of the vertebrate.
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