Animal models of neurological disorders
View Patent ↗The present invention relates to the field of neurological disorders and more particularly to the field of neuropsychiatric disorders. The invention provides non-human, transgenic animal models for brain disorders such as schizophrenia, bipolar disorders, compulsive disorders, addictive disorders and the like. The animals also have applications in the field of GABA neurotransmission and other disorders in which GABA-dependent gene regulation has a role.
1. A transgenic mouse characterized by having reduced expression of a functional non-coding RNA Evf1 or Evf2 or Evf1 and Evf2, wherein the reduced expression is achieved by the introduction of a recombinant nucleic acid construct comprising an Evf sequence having a transcription stop sequence inserted into the Evf sequence, wherein the mouse is homozygous for said insertion, and wherein the mouse exhibits abnormal development of GABAergic interneurons.
2. The transgenic mouse of claim 1 , wherein the mouse has reduced expression of a functional non-coding RNA Evf2.
3. The transgenic mouse of claim 2 , wherein the reduced expression is achieved by the introduction of a recombinant nucleic acid construct comprising an Evf sequence having a transcription stop sequence inserted in exon 1 of the Evf sequence.
4. The transgenic mouse of claim 1 , wherein the mouse exhibits an altered dopamine response in the brain cortex.
5. The transgenic mouse of claim 1 , wherein the mouse has reduced expression of the functional ncRNA Evf2 in a brain tissue.
6. The transgenic mouse of claim 1 , wherein the mouse has reduced expression of the functional ncRNA Evf2 in the hippocampus.
7. A transgenic mouse characterized by having reduced expression of a functional non-coding RNA Evf1 or Evf2 or Evf1 and Evf2, wherein the reduced expression is achieved by the introduction of a recombinant nucleic acid construct comprising an Evf sequence having a transcription stop sequence inserted into the Evf sequence, wherein the mouse is homozygous for said insertion, and wherein the mouse has increased levels of Dlx5 and Dlx6 transcripts.
8. A transgenic mouse characterized by having reduced expression of a functional non-coding RNA Evf1 or Evf2 or Evf1 and Evf2, wherein the reduced expression is achieved by the introduction of a recombinant nucleic acid construct comprising an Evf sequence having a transcription stop sequence inserted into the Evf sequence, wherein the mouse has reduced expression of a functional non-coding RNA Evf2, the reduced expression is achieved by the introduction of a recombinant nucleic acid construct comprising an Evf sequence having a transcription stop sequence inserted in exon 1 of the Evf sequence, wherein the mouse is homozygous for said insertion, and wherein the recombinant nucleic acid construct comprises SEQ ID NO: 1 having a triple polyA sequence inserted between nucleotides 20 and 21 of SEQ ID NO: 1.