Transgenic animals and cell lines for screening drugs effective for the treatment or prevention of Alzheimer's disease
Disclosed are transgenic animals and transfected cell lines expressing a protein associated with Alzheimer's Disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. Also disclosed is the use of such transgenic animals and transfected cell lines to screen potential drug candidates for treating or preventing Alzheimer's disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas. The invention also relates to new antisense oligonucleotides, ribozymes, triplex forming DNA and external guide sequences that can be used to treat or prevent Alzheimer's disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas.
1. A transgenic non-human animal whose germ and somatic cells comprise the DNA molecule of SEQ ID NO:1 or a DNA molecule which is at least 90% homologous thereto, wherein the DNA molecule of SEQ ID NO:1 or a DNA molecule which is at least 90% homologous thereto is over-expressed in one or more cells of said transgenic animal, and wherein the DNA molecule of SEQ ID NO:1 or a DNA molecule which is at least 90% homologous thereto codes for a protein that has an activity of AD7c-NTP when over-expressed in neuronal cells.
2. An in vivo method for screening a candidate drug that is potentially useful for the treatment or prevention of Alzheimer's disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas, said method comprising:
(a) administering a candidate drug to the transgenic animal of claim 1 , and
(b) detecting at least one of the following:
(i) the suppression or prevention of expression of the protein coded for by the DNA molecule contained by said animal; or
(ii) the increased degradation of the protein coded for by the DNA construct contained by said animal;
due to the drug candidate compared to a control animal which has not received the candidate drug.
3. The transgenic non-human animal of claim 1 , wherein said activity of AD7c-NTP possessed by the DNA molecule of SEQ ID NO:1 or a DNA molecule which is at least 90% homologous thereto when over-expressed in neuronal cells is selected from the group consisting of neuritic sprouting, nerve cell death, nerve cell degeneration, neurofibrillary tangles and irregular swollen neurites.
4. An in vivo method for screening a candidate drug that is potentially useful for the treatment or prevention of Alzheimer's disease, neuroectodermal tumors, malignant astrocytomas, and glioblastomas, said method comprising:
(a) administering a candidate drug to the transgenic animal of claim 1 , wherein said transgenic animal exhibits at least one of neuritic sprouting, nerve cell death, degenerating neurons, neurofibrillary tangles, or irregular swollen neurites and axons; and
(b) detecting the reduction of frequency of at least one of neuritic sprouting, nerve cell death, degenerating neurons, neurofibrillary tangles, or irregular swollen neurites and axons in the host due to the drug candidate compared to a control animal which has not received the candidate drug.
5. The method of claim 4 , wherein the DNA construct contained by said animal has SEQ ID NO:1.
6. The transgenic non-human animal of claim 1 , wherein said transgenic animal is a vertebrate.
7. The transgenic non-human animal of claim 1 , wherein said transgenic animal is a mammal.