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Reduced expression of STOP/MAP6 in mice leads to cognitive deficits.

Volle J, Brocard J, Saoud M, Gory-Faure S, Brunelin J, Andrieux A, Suaud-Chagny MF - Schizophr Bull (2012)

Bottom Line: STOP/MAP6 (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia.Results show that the dosage of susceptibility genes modulates their putative phenotypic contribution and that STOP expression has a high penetrance on cognitive abilities.Hence, STOP Het mice might be useful to investigate cognitive defects related to those observed in mental diseases and ultimately might be a valuable experimental model to evaluate preventive treatments.

View Article: PubMed Central - PubMed

Affiliation: Université de Lyon, Lyon, France.

ABSTRACT

Background: STOP/MAP6 (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6 proteins in heterozygous mice (only one allele expressed) would result in abnormal behavior related to those displayed by STOP mice.

Methods: Using a comprehensive test battery, we investigated the behavioral phenotype of STOP heterozygous (Het) mice compared with STOP KO and wild type (WT) mice on animals raised either in standard conditions (controls) or submitted to maternal deprivation.

Results: Control Het mice displayed prominent deficits in social interaction and learning, resembling KO mice. In contrast, they exhibited short-lasting locomotor hyperreactivity to acute mild stress and no impaired locomotor response to amphetamine, much like WT mice. Additionally, perinatal stress deteriorated Het mouse phenotype by exacerbating alterations related to positive symptoms such as their locomotor reactivity to acute mild stress and psychostimulant challenge.

Conclusion: Results show that the dosage of susceptibility genes modulates their putative phenotypic contribution and that STOP expression has a high penetrance on cognitive abilities. Hence, STOP Het mice might be useful to investigate cognitive defects related to those observed in mental diseases and ultimately might be a valuable experimental model to evaluate preventive treatments.

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Related in: MedlinePlus

STOP/MAP6 protein level in control mice. Both MAP6-N and MAP6-E protein levels were lower in heterozygous (Het) STOP mice brain tissue than in wild type (WT). Representative western blot of the amounts of STOP/MAP6 neuronal isoforms (MAP6-N and MAP6-E) present in brain extracts from adult WT, Het, or STOP  (KO) mice. Neuronal Specific Enolase was used as loading control. (Hip, hippocampus; FCx, frontal cortex).
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Figure 1: STOP/MAP6 protein level in control mice. Both MAP6-N and MAP6-E protein levels were lower in heterozygous (Het) STOP mice brain tissue than in wild type (WT). Representative western blot of the amounts of STOP/MAP6 neuronal isoforms (MAP6-N and MAP6-E) present in brain extracts from adult WT, Het, or STOP (KO) mice. Neuronal Specific Enolase was used as loading control. (Hip, hippocampus; FCx, frontal cortex).

Mentions: Total brains or specific brain areas were used to prepare protein extracts. The amounts of MAP6 isoforms (MAP6–N and MAP6-E) in extracts from adult WT or STOP Het mice were evaluated in several independent experiments. As illustrated in figure 1, the expression of both isoforms of MAP6 was lower in STOP Het brain extracts than in WT extracts. The decrease is visible in total-brain extracts, as well as in the hippocampal and prefrontal extracts. This clearly indicated that the gene dosage of STOP/MAP6 resulted in a halved expression of the corresponding proteins.


Reduced expression of STOP/MAP6 in mice leads to cognitive deficits.

Volle J, Brocard J, Saoud M, Gory-Faure S, Brunelin J, Andrieux A, Suaud-Chagny MF - Schizophr Bull (2012)

STOP/MAP6 protein level in control mice. Both MAP6-N and MAP6-E protein levels were lower in heterozygous (Het) STOP mice brain tissue than in wild type (WT). Representative western blot of the amounts of STOP/MAP6 neuronal isoforms (MAP6-N and MAP6-E) present in brain extracts from adult WT, Het, or STOP  (KO) mice. Neuronal Specific Enolase was used as loading control. (Hip, hippocampus; FCx, frontal cortex).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756782&req=5

Figure 1: STOP/MAP6 protein level in control mice. Both MAP6-N and MAP6-E protein levels were lower in heterozygous (Het) STOP mice brain tissue than in wild type (WT). Representative western blot of the amounts of STOP/MAP6 neuronal isoforms (MAP6-N and MAP6-E) present in brain extracts from adult WT, Het, or STOP (KO) mice. Neuronal Specific Enolase was used as loading control. (Hip, hippocampus; FCx, frontal cortex).
Mentions: Total brains or specific brain areas were used to prepare protein extracts. The amounts of MAP6 isoforms (MAP6–N and MAP6-E) in extracts from adult WT or STOP Het mice were evaluated in several independent experiments. As illustrated in figure 1, the expression of both isoforms of MAP6 was lower in STOP Het brain extracts than in WT extracts. The decrease is visible in total-brain extracts, as well as in the hippocampal and prefrontal extracts. This clearly indicated that the gene dosage of STOP/MAP6 resulted in a halved expression of the corresponding proteins.

Bottom Line: STOP/MAP6 (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia.Results show that the dosage of susceptibility genes modulates their putative phenotypic contribution and that STOP expression has a high penetrance on cognitive abilities.Hence, STOP Het mice might be useful to investigate cognitive defects related to those observed in mental diseases and ultimately might be a valuable experimental model to evaluate preventive treatments.

View Article: PubMed Central - PubMed

Affiliation: Université de Lyon, Lyon, France.

ABSTRACT

Background: STOP/MAP6 (KO) mice recapitulate behavioral abnormalities related to positive and negative symptoms and cognitive deficits of schizophrenia. Here, we investigated whether decreased expression of STOP/MAP6 proteins in heterozygous mice (only one allele expressed) would result in abnormal behavior related to those displayed by STOP mice.

Methods: Using a comprehensive test battery, we investigated the behavioral phenotype of STOP heterozygous (Het) mice compared with STOP KO and wild type (WT) mice on animals raised either in standard conditions (controls) or submitted to maternal deprivation.

Results: Control Het mice displayed prominent deficits in social interaction and learning, resembling KO mice. In contrast, they exhibited short-lasting locomotor hyperreactivity to acute mild stress and no impaired locomotor response to amphetamine, much like WT mice. Additionally, perinatal stress deteriorated Het mouse phenotype by exacerbating alterations related to positive symptoms such as their locomotor reactivity to acute mild stress and psychostimulant challenge.

Conclusion: Results show that the dosage of susceptibility genes modulates their putative phenotypic contribution and that STOP expression has a high penetrance on cognitive abilities. Hence, STOP Het mice might be useful to investigate cognitive defects related to those observed in mental diseases and ultimately might be a valuable experimental model to evaluate preventive treatments.

Show MeSH
Related in: MedlinePlus