Phenotypic characterization of C57BL/6J mice carrying the Disc1 gene from the 129S6/SvEv strain

Juan, Liang-Wen; Liao, Chun-Chieh; Lai, Wen-Sung; Chang, Chia‐Yuan; Pei, Ju-Chun; Wong, Wan-Rong; Liu, Chih-Min; Lee, Li-Jen

doi:10.1007/s00429-013-0577-8

Cited by 31 publications

(41 citation statements)

References 59 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Some isoforms of Disc1 are still expressed in mice carrying the deletion 16 . In contrast to the lack of phenotype in our study, the same mutation affected cognitive function and neuronal development on C57BL/6J or mixed C57BL/6J;129S1/SvImJ backgrounds [17][18][19] , indicating the deleted Disc1 gene is not equivalent to the wild-type gene. It is possible that the remaining isoforms are sufficient for retaining a putative sleep-regulatory function, but not other functions of Disc1.…”

Section: Discussioncontrasting

confidence: 99%

See 1 more Smart Citation

The natural DISC1-deletion present in several inbred mouse strains does not affect sleep

2017

View full text Add to dashboard Cite

The gene Disrupted in Schizophrenia-1 (DISC1) is linked to a range of psychiatric disorders. Two recent transgenic studies suggest DISC1 is also involved in homeostatic sleep regulation. Several strains of inbred mice commonly used for genome manipulation experiments, including several Swiss and likely all 129 substrains, carry a natural deletion mutation of Disc1. This constitutes a potential confound for studying sleep in genetically modified mice. Since disturbed sleep can also influence psychiatric and neurodegenerative disease models, this putative confound might affect a wide range of studies in several fields. Therefore, we asked to what extent the natural Disc1 deletion affects sleep. To this end, we first compared sleep and electroencephalogram (EEG) phenotypes of 129S4 mice carrying the Disc1 deletion and C57BL/6N mice carrying the full-length version. We then bred Disc1 from C57BL/6N into the 129S4 background, resulting in S4-Disc1 mice. The differences between 129S4 and C57BL/6N were not detected in the 129S4 to S4-Disc1 comparison. We conclude that the mutation has no effect on the measured sleep and EEG characteristics. Thus, it is unlikely the widespread Disc1 deletion has led to spurious results in previous sleep studies or that it alters sleep in mouse models of psychiatric or neurodegenerative diseases.Many psychiatric disorders, including schizophrenia, major depression, and bipolar disorder, are accompanied by pronounced sleep abnormalities 1, 2 . This was long viewed as a secondary effect downstream of the primary disorder. However, recent evidence suggests that the relation is bidirectional, i.e. sleep problems exacerbate psychiatric diseases [3][4][5][6] . The cause for the high rate of co-occurrence of psychiatric disorders and sleep abnormalities is unknown, but a common genetic predisposition might increase the risk for both 3-5, 7, 8 . A Scottish pedigree with high prevalence of psychiatric disease carries a mutated gene associated with schizophrenia, major depression and bipolar disorder 9 . The gene, known as Disrupted in Schizophrenia-1 (DISC1) encodes an intracellular scaffold protein known to play a role in neuronal development and synaptic function 10 . A role for Disc1 in sleep regulation was suggested in two transgenic studies ectopically expressing human DISC1. In flies human DISC1 caused increased total sleep and increased sleep bout duration whereas in mice it caused increased wakefulness and decreased sleep 11,12 . Although these two reports seem contradictory, it should be noted that flies lack a native Disc1 gene and the transgenic mice expressed both human and mouse Disc1 and that the measurement techniques for flies and mice are necessarily different. Nonetheless, these reports indicate that expression of DISC1 related genes can alter sleep.In contrast to most inbred mouse strains such as C57BL/6, several strains including "Swiss" strains (e.g. FVB, SJL, SWR), and all 129 substrains naturally carry a 25 base pair deletion mutation in exon 6 of Disc1 13-15 . Importantly...

show abstract

Section: Discussioncontrasting

confidence: 99%

“…(email: walker.jackson@dzne. de) abnormalities in behavioral tests, pre-pulse inhibition, neuron morphology, and neuronal excitability [17][18][19] . Thus, the full significance of the deletion remains uncertain.…”

mentioning

confidence: 99%

The natural DISC1-deletion present in several inbred mouse strains does not affect sleep

2017

View full text Add to dashboard Cite

show abstract

“…In patients with schizophrenia, reduced dendritic complexity and spine density in layer III PFC pyramidal neurons have been attributed to deficits in working memory [35,36]. Impaired dendritic architecture has been replicated in the mPFC neurons of animal models of schizophrenia [6,37]. Together, our results demonstrate an anatomical basis for the functional deficits that are induced by prenatal poly I:C exposure.…”

Section: Discussionmentioning

confidence: 51%

“…Disc1 proteins play an important role in various stages of neural development [1,48]. Altered dendritic architecture has been observed in the mPFC and DG neurons of Disc1 knockout mice [37,49]. Together, these results suggest that maternal poly I:C exposure may induce numerous neurochemical changes that affect the developing neurons in the fetal brain and lead to abnormal behaviors in adult poly I:C offspring.…”

Section: Discussionmentioning

confidence: 75%

Prenatal Infection Affects the Neuronal Architecture and Cognitive Function in Adult Mice

Li¹,

Chang²,

Lee

et al. 2014

Dev Neurosci

Self Cite

View full text Add to dashboard Cite

Environmental factors such as prenatal infection are involved in the pathogenic processes of neurodevelopmental psychiatric disorders. In the present study, we administered a viral mimic, polyriboinosinic-polyribocytidylic acid (poly I:C, 20 mg/kg, i.p.), to pregnant B6 mice at gestational day 9.5. Neonates born to these poly I:C-treated dams showed an increase of microglia in the hippocampus, indicating an activation of the immune system in the brains. Moreover, a significant increase in the number of dopamine-producing neurons in the ventral tegmental area was observed in adult male poly I:C offspring compared with age-matched saline offspring. Poly I:C offspring also exhibited hypolocomotor activity in a novel open-field arena but did not display signs of anxiety or depression in the elevated plus maze or the forced swim test, respectively. However, the short-term memory of the poly I:C offspring was impaired in a novel object recognition task. Therefore, the dendritic architecture of granule cells in the dentate gyrus (DG) and pyramidal neurons in the medial prefrontal cortex (mPFC) were examined. The dendritic complexity was reduced in the DG granule cells of the poly I:C offspring and exhibited shorter dendritic length compared with the saline offspring. The density of dendritic spines in the DG granule cells was also decreased in the poly I:C offspring. Furthermore, the dendritic complexity and spine density were reduced in layer II/III mPFC pyramidal neurons of the poly I:C offspring. Together, these data demonstrate impaired short-term memory and altered dendritic architecture in adult poly I:C offspring, which validates the prenatal infection paradigm as a model for neurodevelopmental psychiatric disorders.

show abstract

“…Local network connectivity has previously been reported to be altered in other models of altered DISC1 function. 57, 58, 59 To examine the effect of truncated Disc1 in Disc1tr Hemi mice, we recorded spontaneous excitatory postsynaptic currents (sEPSCs) under voltage clamp conditions from Wt and Disc1tr Hemi pyramidal neurons. Although the probability distribution of the amplitude of sEPSCs was similar in Wt and Disc1tr Hemi neurons ( P =0.34, Kolmogorov–Smirnov test), the distribution of the inter-event intervals of the sEPSCs was significantly decreased in Disc1tr Hemi mice (Figures 3c, P <0.05, Kolmogorov–Smirnov test).…”

Section: Resultsmentioning

confidence: 99%

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

et al. 2015

View full text Add to dashboard Cite

Considerable evidence implicates DISC1 as a susceptibility gene for multiple psychiatric diseases. DISC1 has been intensively studied at the molecular, cellular and behavioral level, but its role in regulating brain connectivity and brain network function remains unknown. Here, we utilize a set of complementary approaches to assess the functional brain network abnormalities present in mice expressing a truncated Disc1 gene (Disc1tr Hemi mice). Disc1tr Hemi mice exhibited hypometabolism in the prefrontal cortex (PFC) and reticular thalamus along with a reorganization of functional brain network connectivity that included compromised hippocampal–PFC connectivity. Altered hippocampal–PFC connectivity in Disc1tr Hemi mice was confirmed by electrophysiological analysis, with Disc1tr Hemi mice showing a reduced probability of presynaptic neurotransmitter release in the monosynaptic glutamatergic hippocampal CA1–PFC projection. Glutamate system dysfunction in Disc1tr Hemi mice was further supported by the attenuated cerebral metabolic response to the NMDA receptor (NMDAR) antagonist ketamine and decreased hippocampal expression of NMDAR subunits 2A and 2B in these animals. These data show that the Disc1 truncation in Disc1tr Hemi mice induces a range of translationally relevant endophenotypes underpinned by glutamate system dysfunction and altered brain connectivity.

show abstract

Phenotypic characterization of C57BL/6J mice carrying the Disc1 gene from the 129S6/SvEv strain

Cited by 31 publications

References 59 publications

The natural DISC1-deletion present in several inbred mouse strains does not affect sleep

The natural DISC1-deletion present in several inbred mouse strains does not affect sleep

Prenatal Infection Affects the Neuronal Architecture and Cognitive Function in Adult Mice

Altered functional brain network connectivity and glutamate system function in transgenic mice expressing truncated Disrupted-in-Schizophrenia 1

Contact Info

Product

Resources

About