AI Article Synopsis
- - The DISC1 gene has been linked to various neuropsychiatric disorders, particularly schizophrenia, as it undergoes disruption due to a chromosomal translocation affecting chromosomes 1 and 11 in a Scottish family with a high prevalence of these disorders.
- - Research into mouse models that contain modifications of the DISC1 gene, particularly the 129 mouse strain with a natural 25bp deletion, has revealed significant effects on the gene's expression, notably a decrease in full-length DISC1 levels in the hippocampus.
- - Behavioral studies on heterozygous 129DISC1(Del) mice show altered activity levels (hyperactivity in males and hypoactivity in females), deficits in pre-pulse inhibition, and increased despair behavior, demonstrating
Article Abstract
Disrupted in schizophrenia-1 (DISC1) gene is associated with several neuropsychiatric disorders as it is disrupted by a balanced translocation involving chromosomes 1 and 11 in a large Scottish pedigree with high prevalence of schizophrenia, bipolar disorder and major depression. Since its identification, several mouse models with DISC1 genetic modifications have been generated using different approaches. Interestingly, a natural deletion of 25bp in the 129 mouse strain alters the DISC1 gene reading frame leading to a premature stop codon very close to the gene breakpoint in the mutant allele of the Scottish family. In the present study we confirmed that the 129DISC1(Del) mutation results in reduced level of full length DISC1 in hippocampus of heterozygous mice and we have characterized the behavioral consequences of heterozygous 129DISC1(Del) mutation in a mixed B6129 genetic background. We found alterations in spontaneous locomotor activity (hyperactivity in males and hypoactivity in females), deficits in pre-pulse inhibition (PPI) and also increased despair behavior in heterozygous 129DISC1(Del) mice, thus reproducing typical behaviors associated to psychiatric disorders. Since this mouse strain is widely and commercially available, we propose it as an amenable tool to study DISC1-related biochemical alterations and psychiatric behaviors.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4115618 | PMC |
| http://dx.doi.org/10.3389/fnbeh.2014.00253 | DOI Listing |
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