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Loss of the SV2-like protein SVOP produces no apparent deficits in laboratory mice.

Yao J, de la Iglesia HO, Bajjalieh SM - PLoS ONE (2013)

Bottom Line: Because significant levels of neurotransmission remain in the absence of SV2 it has been proposed that SVOP performs a function similar to that of SV2 that mitigates the phenotype of SV2 knockout mice.SVOP/SV2A/SV2B triple knockout mice did not display a phenotype more severe than mice harboring the SV2A/SV2B gene deletions.These findings support the interpretation that SVOP performs a unique, though subtle, function that is not necessary for survival under normal conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Neurons express two families of transporter-like proteins - Synaptic Vesicle protein 2 (SV2A, B, and C) and SV2-related proteins (SVOP and SVOPL). Both families share structural similarity with the Major Facilitator (MF) family of transporters. SV2 is present in all neurons and endocrine cells, consistent with it playing a key role in regulated exocytosis. Like SV2, SVOP is expressed in all brain regions, with highest levels in cerebellum, hindbrain and pineal gland. Furthermore, SVOP is expressed earlier in development than SV2 and is one of the neuronal proteins whose expression declines most during aging. Although SV2 is essential for survival, it is not required for development. Because significant levels of neurotransmission remain in the absence of SV2 it has been proposed that SVOP performs a function similar to that of SV2 that mitigates the phenotype of SV2 knockout mice. To test this, we generated SVOP knockout mice and SVOP/SV2A/SV2B triple knockout mice. Mice lacking SVOP are viable, fertile and phenotypically normal. Measures of neurotransmission and behaviors dependent on the cerebellum and pineal gland revealed no measurable phenotype. SVOP/SV2A/SV2B triple knockout mice did not display a phenotype more severe than mice harboring the SV2A/SV2B gene deletions. These findings support the interpretation that SVOP performs a unique, though subtle, function that is not necessary for survival under normal conditions.

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Loss of SVOP does not affect motor coordination.Mice were tested for motor coordination on the rotating rod. Twelve SVOP knockout (-/-) mice and 12 SVOP wild type (+/+) littermates were included in the test. Shown are average fall latencies across 12 trials (3 trials per day over 4 consecutive days). Each data point represents the group mean± SEM. Performance between groups did not differ (Students t test, p values ranged from 0.17 to 0.98 across trials, SAS software analysis (GLIMMIX) generalized linear mixed analysis of intra-individual correlation over time, P=0.90). Therefore, loss of SVOP did not affect motor performance.
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pone-0068215-g006: Loss of SVOP does not affect motor coordination.Mice were tested for motor coordination on the rotating rod. Twelve SVOP knockout (-/-) mice and 12 SVOP wild type (+/+) littermates were included in the test. Shown are average fall latencies across 12 trials (3 trials per day over 4 consecutive days). Each data point represents the group mean± SEM. Performance between groups did not differ (Students t test, p values ranged from 0.17 to 0.98 across trials, SAS software analysis (GLIMMIX) generalized linear mixed analysis of intra-individual correlation over time, P=0.90). Therefore, loss of SVOP did not affect motor performance.

Mentions: The cerebellum plays an important role in motor control, and cerebellar deficits result in decreased motor coordination [27]. We assessed motor coordination in SVOP mutant mice by comparing their performance to wild-type mice on the rotating rod [27]. SVOP-/- mice and age- and gender-matched wild type littermates, 8-10 weeks of age, were tested on an accelerating rotarod three times per day for four days. We observed no significant difference in baseline performance (first trial, latency to fall: SVOP +/+ 85.5±8.6s, SVOP -/- 101.9±9.5s, p=0.22, two-tailed student t test) (Figure 6). Mice from both genotypes also demonstrated motor learning as indicated by increasing latency to fall across trials (GLIMMIX analysis of distributions, p=0.90). These results indicate that loss of SVOP does not impair cerebellar functioning or motor learning, consistent with SVOP being non-essential to neurotransmission in the cerebellum.


Loss of the SV2-like protein SVOP produces no apparent deficits in laboratory mice.

Yao J, de la Iglesia HO, Bajjalieh SM - PLoS ONE (2013)

Loss of SVOP does not affect motor coordination.Mice were tested for motor coordination on the rotating rod. Twelve SVOP knockout (-/-) mice and 12 SVOP wild type (+/+) littermates were included in the test. Shown are average fall latencies across 12 trials (3 trials per day over 4 consecutive days). Each data point represents the group mean± SEM. Performance between groups did not differ (Students t test, p values ranged from 0.17 to 0.98 across trials, SAS software analysis (GLIMMIX) generalized linear mixed analysis of intra-individual correlation over time, P=0.90). Therefore, loss of SVOP did not affect motor performance.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3722232&req=5

pone-0068215-g006: Loss of SVOP does not affect motor coordination.Mice were tested for motor coordination on the rotating rod. Twelve SVOP knockout (-/-) mice and 12 SVOP wild type (+/+) littermates were included in the test. Shown are average fall latencies across 12 trials (3 trials per day over 4 consecutive days). Each data point represents the group mean± SEM. Performance between groups did not differ (Students t test, p values ranged from 0.17 to 0.98 across trials, SAS software analysis (GLIMMIX) generalized linear mixed analysis of intra-individual correlation over time, P=0.90). Therefore, loss of SVOP did not affect motor performance.
Mentions: The cerebellum plays an important role in motor control, and cerebellar deficits result in decreased motor coordination [27]. We assessed motor coordination in SVOP mutant mice by comparing their performance to wild-type mice on the rotating rod [27]. SVOP-/- mice and age- and gender-matched wild type littermates, 8-10 weeks of age, were tested on an accelerating rotarod three times per day for four days. We observed no significant difference in baseline performance (first trial, latency to fall: SVOP +/+ 85.5±8.6s, SVOP -/- 101.9±9.5s, p=0.22, two-tailed student t test) (Figure 6). Mice from both genotypes also demonstrated motor learning as indicated by increasing latency to fall across trials (GLIMMIX analysis of distributions, p=0.90). These results indicate that loss of SVOP does not impair cerebellar functioning or motor learning, consistent with SVOP being non-essential to neurotransmission in the cerebellum.

Bottom Line: Because significant levels of neurotransmission remain in the absence of SV2 it has been proposed that SVOP performs a function similar to that of SV2 that mitigates the phenotype of SV2 knockout mice.SVOP/SV2A/SV2B triple knockout mice did not display a phenotype more severe than mice harboring the SV2A/SV2B gene deletions.These findings support the interpretation that SVOP performs a unique, though subtle, function that is not necessary for survival under normal conditions.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology, University of Washington, Seattle, Washington, United States of America.

ABSTRACT
Neurons express two families of transporter-like proteins - Synaptic Vesicle protein 2 (SV2A, B, and C) and SV2-related proteins (SVOP and SVOPL). Both families share structural similarity with the Major Facilitator (MF) family of transporters. SV2 is present in all neurons and endocrine cells, consistent with it playing a key role in regulated exocytosis. Like SV2, SVOP is expressed in all brain regions, with highest levels in cerebellum, hindbrain and pineal gland. Furthermore, SVOP is expressed earlier in development than SV2 and is one of the neuronal proteins whose expression declines most during aging. Although SV2 is essential for survival, it is not required for development. Because significant levels of neurotransmission remain in the absence of SV2 it has been proposed that SVOP performs a function similar to that of SV2 that mitigates the phenotype of SV2 knockout mice. To test this, we generated SVOP knockout mice and SVOP/SV2A/SV2B triple knockout mice. Mice lacking SVOP are viable, fertile and phenotypically normal. Measures of neurotransmission and behaviors dependent on the cerebellum and pineal gland revealed no measurable phenotype. SVOP/SV2A/SV2B triple knockout mice did not display a phenotype more severe than mice harboring the SV2A/SV2B gene deletions. These findings support the interpretation that SVOP performs a unique, though subtle, function that is not necessary for survival under normal conditions.

Show MeSH
Related in: MedlinePlus