Specificity of behavioral and neurochemical dysfunction in the chakragati mouse: a novel genetic model of a movement disorder

Fitzgerald, Lawrence W.; Ratty, Anil K.; Teitler, Milt; Gross, Kenneth W.; Glick, Stanley D.

doi:10.1016/0006-8993(93)91465-5

Cited by 29 publications

(11 citation statements)

References 54 publications

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“…Mice exhibit spontaneous motor stereotypies, including circling, jumping, backflips and self-grooming 86,136–138 . Scoring of stereotypies is conducted most reliably by an investigator observing video taped sessions or in real time.…”

Section: Assays For Repetitive Behavioursmentioning

confidence: 99%

Behavioural phenotyping assays for mouse models of autism

et al. 2010

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Autism is a heterogeneous neurodevelopmental disorder of unknown aetiology that affects 1 in 100–150 individuals. Diagnosis is based on three categories of behavioural criteria: abnormal social interactions, communication deficits and repetitive behaviours. Strong evidence for a genetic basis has prompted the development of mouse models with targeted mutations in candidate genes for autism. As the diagnostic criteria for autism are behavioural, phenotyping these mouse models requires behavioural assays with high relevance to each category of the diagnostic symptoms. Behavioural neuroscientists are generating a comprehensive set of assays for social interaction, communication and repetitive behaviours to test hypotheses about the causes of austism. Robust phenotypes in mouse models hold great promise as translational tools for discovering effective treatments for components of autism spectrum disorders.

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Section: Assays For Repetitive Behavioursmentioning

confidence: 99%

Behavioural phenotyping assays for mouse models of autism

et al. 2010

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“…DA and NE show gender-specific alterations and rapid age-related declines (Steger et al 1991(Steger et al , 1993Bartke et al 1994Bartke et al , 1999Cecim et al 1996). Modulators of locomotion and/or circling include adenosine, ACh, 5-HT, thyroid stimulating hormone, SRIF, orexins, glutamate and especially DA (Blackburn et al 1984;Koshikawa et al 1990;Fitzgerald et al 1993;Fedrowitz et al 2000;Nakamura et al 2000;Kincaid 2001;Hathway et al 2003;Isaac and Berridge 2003). DA also modulates libido which is low in Tg (Szczypka et al 1998).…”

Section: Neuroendocrine Distortion Hypothesismentioning

confidence: 96%

“…Lack of obvious vestibular abnormalities and intact hearing suggests that hyperactivity and rotation in Cr traces to the central nervous system. Circling Chakragati and Coloboma mice and circling ci3 rats also have central nervous system alterations (Fitzgerald et al 1992(Fitzgerald et al , 1993Hess et al 1996;Torres et al 2004;Schirmer et al 2007). The appearance of some selected Cr with small or absent eyes suggests that ion channel alterations (particularly K ? )…”

Section: Learned Stereotypies?mentioning

confidence: 96%

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Modifier Selection by Transgenes: The Case of Growth Hormone Transgenesis and Hyperactive Circling Mice

et al. 2008

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Deleterious impacts of major mutations can be ameliorated by stabilising selection acting on modifier genes. We hypothesise that a new hyperactive circling mouse (counterspin: Cr) arises when modifier genes inadvertently selected to ameliorate the negative impacts of a growth hormone transgenic insertion segregate into the normal genetic background that lacks the transgene. We hypothesise that such modifiers generate a phenotype ''mirror image'' to the transgenics on the otherwise normal background. We highlight this by testing a priori hypotheses that counterspin and transgenic growth hormone mice deviate oppositely from normal mice across a broad spectrum of characteristics. Results spanning growth, sensorimotor performance, cognition and striatal neurotransmitters provide strong circumstantial evidence for the hypothesis. In a more direct test for selection in the transgenic mice, we found that those examined in 2008 slept *3 h/d less than they did 14 years ago (P \ 0.0005). This is a profound change strongly supporting the reality of modifier selection in these mice. Our results highlight that modifiers may act powerfully on genetically engineered constructs given a genetically variable background. Furthermore, we suggest that modifier selection might provide a novel method for deriving genetic models, and specifically, models phenotypically opposite to engineered constructs or natural mutations.

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“…For instance, the mouse mutant shows behavioral abnormalities, including novelty-driven hyperactivity that is manifested as increased circling activity in the open field (Ratty et al, 1990;Torres et al, 2004;Torres et al, 2005a). Further, ckr mice show asymmetric elevations of dopamine (DA) D 2 -like receptors in basal ganglia circuitry (Fitzgerald et al, 1993), and high-resolution magnetic resonance imaging (MRI) of these mutants indicates selective enlargement of the lateral ventricles (Torres et al, 2004). As these abnormalities are often diagnosed in patients with schizophrenia, genetically mutant ckr mice might be relevant for understanding or pinpointing psychoses-causing mechanisms.…”

Section: Introductionmentioning

confidence: 99%

Magnetic resonance imaging and spectroscopy in a mouse model of schizophrenia

Torres

Hallas

Gross

et al. 2008

Brain Research Bulletin

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Metabolic brain abnormalities, as demonstrated by 1 H-magnetic resonance spectroscopy techniques, are common occurrences in adult schizophrenia. As mice share important biochemical and genomic similarities with humans, we tested whether brain metabolic abnormalities also occur in a transgenic mouse model of schizophrenia. In vivo 1 H-magnetic resonance spectroscopy at 4.7 T of the chakragati mouse brain revealed abnormalities in relative levels of choline 3.20 ppm and Nacetylaspartate 2.01 ppm compounds. These results are consistent with a prior proposal that deficits in metabolite ratios may be common features of psychotic disorders. Thus, chakragati mice recapitulate certain aspects of the human disease phenotype and further support the utility of this animal model for understanding causal factors underlying uniquely human brain diseases.

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Specificity of behavioral and neurochemical dysfunction in the chakragati mouse: a novel genetic model of a movement disorder

Cited by 29 publications

References 54 publications

Behavioural phenotyping assays for mouse models of autism

Behavioural phenotyping assays for mouse models of autism

Modifier Selection by Transgenes: The Case of Growth Hormone Transgenesis and Hyperactive Circling Mice

Magnetic resonance imaging and spectroscopy in a mouse model of schizophrenia

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