2007
DOI: 10.1016/j.neuron.2007.04.015
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Behavioral Phenotypes of Disc1 Missense Mutations in Mice

Abstract: To support the role of DISC1 in human psychiatric disorders, we identified and analyzed two independently derived ENU-induced mutations in Exon 2 of mouse Disc1. Mice with mutation Q31L showed depressive-like behavior with deficits in the forced swim test and other measures that were reversed by the antidepressant bupropion, but not by rolipram, a phosphodiesterase-4 (PDE4) inhibitor. In contrast, L100P mutant mice exhibited schizophrenic-like behavior, with profound deficits in prepulse inhibition and latent … Show more

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Cited by 494 publications
(538 citation statements)
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References 85 publications
(130 reference statements)
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“…51 100P mutant mice exhibit schizophrenia-like behaviour, with profound deficits in prepulse inhibition (PPI) and latent inhibition (LI), measures of sensory motor gating and attention, which are reversed by treatment with typical or atypical antipsychotics. 50 Mice with the 31L mutation also show LI deficits, but by contrast to 100P, show modest PPI deficits and a more depressive-like behaviour with a pronounced deficit (not seen in the 100P strain) in the forced swim test, a measure of despair. 50 The 31L deficit is partially reversed by the antidepressant bupropion, but not by rolipram, a phosphodiesterase 4 (PDE4) inhibitor.…”
Section: The Phenotype Of Mouse Disc1 Variantsmentioning
confidence: 99%
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“…51 100P mutant mice exhibit schizophrenia-like behaviour, with profound deficits in prepulse inhibition (PPI) and latent inhibition (LI), measures of sensory motor gating and attention, which are reversed by treatment with typical or atypical antipsychotics. 50 Mice with the 31L mutation also show LI deficits, but by contrast to 100P, show modest PPI deficits and a more depressive-like behaviour with a pronounced deficit (not seen in the 100P strain) in the forced swim test, a measure of despair. 50 The 31L deficit is partially reversed by the antidepressant bupropion, but not by rolipram, a phosphodiesterase 4 (PDE4) inhibitor.…”
Section: The Phenotype Of Mouse Disc1 Variantsmentioning
confidence: 99%
“…50 Mice with the 31L mutation also show LI deficits, but by contrast to 100P, show modest PPI deficits and a more depressive-like behaviour with a pronounced deficit (not seen in the 100P strain) in the forced swim test, a measure of despair. 50 The 31L deficit is partially reversed by the antidepressant bupropion, but not by rolipram, a phosphodiesterase 4 (PDE4) inhibitor. This study demonstrates that Disc1 missense mutations in mice give rise to depression-like (31L) and schizophrenia-like (100P) phenotypes, thus further supporting the role of this gene in major mental illness.…”
Section: The Phenotype Of Mouse Disc1 Variantsmentioning
confidence: 99%
See 2 more Smart Citations
“…While the roles of these variants are still not known, recent studies using mice deficient in PDE4B have shown that this subfamily plays a complementary role in the control of neutrophil function (Ariga et al, 2004) and is required for antipsychotic effects of rolipram (Siuciak et al, 2007). In addition, PDE4B also is involved in schizophrenia by interacting with the DISC1 gene, a candidate susceptibility factor for schizophrenia (Clapcote et al, 2007;Millar et al, 2005). These results indicate that PDE4B plays a significant role in CNS functions.…”
Section: Introductionmentioning
confidence: 99%