Transgenic pig model for a hereditary neurodegenerative autosomal dominant disease
AssigneeAarhus Universitet
InventorsLone Bruhn Madsen, Christian Bendixen, Knud Larsen, Connie Jakobsen Juhl, Bo Thomsen
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Abstract
The present invention discloses a non-human animal model for a hereditary autosomal dominant disease. The non-human animal model expresses at least one phenotype associated with the disease and is obtained by a genetic determinant. The invention also relates to sperm cells and embryos comprising the genetic determinant for an autosomal dominant disease. Furthermore, methods for producing the non-human animal model, sperm cell, and embryos are disclosed.
Claims22
A transgenic pig model for a hereditary neurodegenerative autosomal dominant disease, comprising a transgenic pig whose genome comprises a DNA sequence encoding a protein involved in the development of a hereditary neurodeqenerative autosomal dominant disease, wherein the transgenic pig expresses the protein in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue.
A method for producing a transgenic pig model for a hereditary neurodegenerative autosomal dominant disease, comprising a transgenic pig whose genome comprises a DNA sequence encoding a protein involved in the development of a hereditary neurodeqenerative autosomal dominant disease, wherein the transgenic pig expresses the protein in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue, said method comprising the steps of:
- i) providing semen from a male pig,
- ii) providing a DNA sequence encoding a protein involved in the development of a hereditary neurodegenerative autosomal dominant disease,
- iii) contacting said semen and said DNA sequence,
- iv) fertilising an oocyte from a female pig with the semen and the genetic material, and
- v) incubating said fertilised oocyte under conditions allowing said fertilised oocyte to develop into said transgenic pig, wherein the transgenic pig expresses the protein in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue.
A method for evaluating the response of a therapeutical treatment of a hereditary disease, said method comprising the steps of:
- a. providing a transgenic pig model for a hereditary neurodegenerative autosomal dominant disease, comprising a transgenic pig whose genome comprises a DNA sequence encoding a protein involved in the development of a hereditary neurodeqenerative autosomal dominant disease, wherein the transgenic pig expresses the protein in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue,
- b. treating said pig with at least one pharmaceutical composition exerting an effect on the reduction in the number of neurons in the nerve tissue or the accumulation of protein aggregates in the nerve tissue, and
- c. evaluating the effect observed.
A transgenic pig sperm cell comprising a DNA sequence encoding a protein involved in the development of a hereditary neurodegenerative autosomal dominant disease wherein said protein is expressed in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue when expressed in a pig host organism.
A method for producing a transgenic pig sperm cell comprising a DNA sequence encoding a protein involved in the development of a hereditary neurodegenerative autosomal dominant disease, wherein said protein is expressed in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue when expressed in a pig host organism, said method comprising the steps of:
- a. providing a pig sperm cell,
- b. providing a DNA sequence encoding a protein involved in the development of a hereditary neurodeqenerative autosomal dominant disease wherein said protein is expressed in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue when expressed in a pig host organism, and
- c. contacting said pig sperm cell and said DNA sequence, wherein said contacting results in the uptake of the DNA sequence into the pig sperm cell.
A method for fertilising an oocyte by sperm-mediated gene transfer, said method comprising the step of providing a composition comprising a pig sperm cell in combination with a DNA sequence encoding a protein involved in the development of an hereditary neurodegenerative autosomal dominant disease wherein said protein is expressed in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue when expressed in a pig host organism.
A transgenic embryo obtained by fertilising an oocyte with a pig sperm cell comprising a DNA sequence encoding a protein involved in the development of a hereditary neurodegenerative autosomal dominant disease wherein said protein is expressed in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue when expressed in a pig host organism.
A transgenic embryo obtained by fertilising an oocyte with a composition comprising a DNA sequence encoding a protein involved in the development of a hereditary neurodegenerative autosomal dominant disease, wherein said protein is expressed in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue when expressed in a pig host organism.
A method for the cultivation and development of a transgenic embryo obtained by fertilising an oocyte with a pig sperm cell comprising a DNA sequence encoding a protein involved in the development of a hereditary neurodegenerative autosomal dominant disease, said method comprising the step of cultivating said embryo under conditions allowing the embryo to develop into a pig offspring expressing said protein in nerve tissue and exhibiting a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue.
A method for screening the efficacy of a pharmaceutical composition, said method comprising the steps of:
- a. providing a transgenic pig model for a hereditary neurodegenerative autosomal dominant disease, comprising a transgenic pig whose genome comprises a DNA sequence encoding a protein involved in the development of a hereditary neurodegenerative autosomal dominant disease, wherein the transgenic pig expresses the protein in nerve tissue and exhibits a reduction in the number of neurons in the nerve tissue and an accumulation of protein aggregates in the nerve tissue,
- b. expressing in said pig model said DNA sequence involved in the development of a hereditary neurodegenerative autosomal dominant disease,
- c. administering to said pig the pharmaceutical composition, the efficacy of which is to be evaluated, and
- d. evaluating the effect, if any, of the pharmaceutical composition on the reduction in the number of neurons in the nerve tissue or the accumulation of protein aggregates in the nerve tissue exerted by the DNA sequence when expressed in the pig model.
Dependencies are inferred from the claim text.