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Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome.

Allensworth M, Saha A, Reiter LT, Heck DH - BMC Genet. (2011)

Bottom Line: The majority of AS cases are due to loss of the maternal copy of the UBE3A gene.Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range.These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38139, USA.

ABSTRACT

Background: Angelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with mental retardation, a generally happy disposition, ataxia and characteristic behaviors such as inappropriate laughter, social-seeking behavior and hyperactivity. The majority of AS cases are due to loss of the maternal copy of the UBE3A gene. Maternal Ube3a deficiency (Ube3a m-/p+), as well as complete loss of Ube3a expression (Ube3a m-/p-), have been reproduced in the mouse model used here.

Results: Here we asked if two characteristic AS phenotypes - social-seeking behavior and hyperactivity - are reproduced in the Ube3a deficient mouse model of AS. We quantified social-seeking behavior as time spent in close proximity to a stranger mouse and activity as total time spent moving during exploration, movement speed and total length of the exploratory path. Mice of all three genotypes (Ube3a m+/p+, Ube3a m-/p+, Ube3a m-/p-) were tested and found to spend the same amount of time in close proximity to the stranger, indicating that Ube3a deficiency in mice does not result in increased social seeking behavior or social dis-inhibition. Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range.

Conclusions: Although hyperactivity and social-seeking behavior are characteristic phenotypes of Angelman Syndrome in humans, the Ube3a deficient mouse model does not reproduce these phenotypes in comparison to their wild-type littermates. These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.

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Three-dimensional and color coded visualizations of different aspects of exploratory behavior. Three aspects of exploratory behavior are shown under control conditions (A-I) and under test conditions, i.e. with a stranger mouse present in the cage marked with "S" (J-R). Each panel covers the entire arena. Data for Ube3am-/p-, Ube3am-/p+ and wild-type mice are shown in the left, middle and right columns respectively. All behavioral variables visualized here for qualitative comparison were also compared quantitatively (see text for details). (A-C and J-L) "Time vs. Position" plots illustrate the position of the animal over time with time increasing along the z-axis. Movement paths recorded under control and test conditions are shown in (A-C) and (J-L) respectively. Duration (i.e. the time spent at any given site along the path) is represented in color-coded maps for control and test conditions in panels (D-F) and (M-O) respectively. Sites where mice lingered for ~60 seconds or more show up as red and purple spots (the two black arrows in (D) point at two examples of such sites). The speed with which mice moved along their exploratory path is shown in color-coded maps for control and test conditions in panels (G-I) and (P-R) respectively. The color scale for duration is time in seconds. The color scale for speed is in cm/sec.
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Figure 2: Three-dimensional and color coded visualizations of different aspects of exploratory behavior. Three aspects of exploratory behavior are shown under control conditions (A-I) and under test conditions, i.e. with a stranger mouse present in the cage marked with "S" (J-R). Each panel covers the entire arena. Data for Ube3am-/p-, Ube3am-/p+ and wild-type mice are shown in the left, middle and right columns respectively. All behavioral variables visualized here for qualitative comparison were also compared quantitatively (see text for details). (A-C and J-L) "Time vs. Position" plots illustrate the position of the animal over time with time increasing along the z-axis. Movement paths recorded under control and test conditions are shown in (A-C) and (J-L) respectively. Duration (i.e. the time spent at any given site along the path) is represented in color-coded maps for control and test conditions in panels (D-F) and (M-O) respectively. Sites where mice lingered for ~60 seconds or more show up as red and purple spots (the two black arrows in (D) point at two examples of such sites). The speed with which mice moved along their exploratory path is shown in color-coded maps for control and test conditions in panels (G-I) and (P-R) respectively. The color scale for duration is time in seconds. The color scale for speed is in cm/sec.

Mentions: Representative examples of exploratory behavior of Ube3a deficient and wild-type mice under control and test conditions (without and with a stranger mouse present, respectively) are visualized for qualitative comparison in Figure 2 as movement path vs. time plots (Figure 2A-C, J-L), and color maps for duration (Figure 2D-F, M-O) and movement speed (Figure 2G-I, P-R). Quantitative comparisons are shown in subsequent figures.


Normal social seeking behavior, hypoactivity and reduced exploratory range in a mouse model of Angelman syndrome.

Allensworth M, Saha A, Reiter LT, Heck DH - BMC Genet. (2011)

Three-dimensional and color coded visualizations of different aspects of exploratory behavior. Three aspects of exploratory behavior are shown under control conditions (A-I) and under test conditions, i.e. with a stranger mouse present in the cage marked with "S" (J-R). Each panel covers the entire arena. Data for Ube3am-/p-, Ube3am-/p+ and wild-type mice are shown in the left, middle and right columns respectively. All behavioral variables visualized here for qualitative comparison were also compared quantitatively (see text for details). (A-C and J-L) "Time vs. Position" plots illustrate the position of the animal over time with time increasing along the z-axis. Movement paths recorded under control and test conditions are shown in (A-C) and (J-L) respectively. Duration (i.e. the time spent at any given site along the path) is represented in color-coded maps for control and test conditions in panels (D-F) and (M-O) respectively. Sites where mice lingered for ~60 seconds or more show up as red and purple spots (the two black arrows in (D) point at two examples of such sites). The speed with which mice moved along their exploratory path is shown in color-coded maps for control and test conditions in panels (G-I) and (P-R) respectively. The color scale for duration is time in seconds. The color scale for speed is in cm/sec.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3025901&req=5

Figure 2: Three-dimensional and color coded visualizations of different aspects of exploratory behavior. Three aspects of exploratory behavior are shown under control conditions (A-I) and under test conditions, i.e. with a stranger mouse present in the cage marked with "S" (J-R). Each panel covers the entire arena. Data for Ube3am-/p-, Ube3am-/p+ and wild-type mice are shown in the left, middle and right columns respectively. All behavioral variables visualized here for qualitative comparison were also compared quantitatively (see text for details). (A-C and J-L) "Time vs. Position" plots illustrate the position of the animal over time with time increasing along the z-axis. Movement paths recorded under control and test conditions are shown in (A-C) and (J-L) respectively. Duration (i.e. the time spent at any given site along the path) is represented in color-coded maps for control and test conditions in panels (D-F) and (M-O) respectively. Sites where mice lingered for ~60 seconds or more show up as red and purple spots (the two black arrows in (D) point at two examples of such sites). The speed with which mice moved along their exploratory path is shown in color-coded maps for control and test conditions in panels (G-I) and (P-R) respectively. The color scale for duration is time in seconds. The color scale for speed is in cm/sec.
Mentions: Representative examples of exploratory behavior of Ube3a deficient and wild-type mice under control and test conditions (without and with a stranger mouse present, respectively) are visualized for qualitative comparison in Figure 2 as movement path vs. time plots (Figure 2A-C, J-L), and color maps for duration (Figure 2D-F, M-O) and movement speed (Figure 2G-I, P-R). Quantitative comparisons are shown in subsequent figures.

Bottom Line: The majority of AS cases are due to loss of the maternal copy of the UBE3A gene.Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range.These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Anatomy and Neurobiology, University of Tennessee Health Science Center, Memphis, TN 38139, USA.

ABSTRACT

Background: Angelman syndrome (AS) is a neurogenetic disorder characterized by severe developmental delay with mental retardation, a generally happy disposition, ataxia and characteristic behaviors such as inappropriate laughter, social-seeking behavior and hyperactivity. The majority of AS cases are due to loss of the maternal copy of the UBE3A gene. Maternal Ube3a deficiency (Ube3a m-/p+), as well as complete loss of Ube3a expression (Ube3a m-/p-), have been reproduced in the mouse model used here.

Results: Here we asked if two characteristic AS phenotypes - social-seeking behavior and hyperactivity - are reproduced in the Ube3a deficient mouse model of AS. We quantified social-seeking behavior as time spent in close proximity to a stranger mouse and activity as total time spent moving during exploration, movement speed and total length of the exploratory path. Mice of all three genotypes (Ube3a m+/p+, Ube3a m-/p+, Ube3a m-/p-) were tested and found to spend the same amount of time in close proximity to the stranger, indicating that Ube3a deficiency in mice does not result in increased social seeking behavior or social dis-inhibition. Also, Ube3a deficient mice were hypoactive compared to their wild-type littermates as shown by significantly lower levels of activity, slower movement velocities, shorter exploratory paths and a reduced exploratory range.

Conclusions: Although hyperactivity and social-seeking behavior are characteristic phenotypes of Angelman Syndrome in humans, the Ube3a deficient mouse model does not reproduce these phenotypes in comparison to their wild-type littermates. These phenotypic differences may be explained by differences in the size of the genetic defect as ~70% of AS patients have a deletion that includes several other genes surrounding the UBE3A locus.

Show MeSH
Related in: MedlinePlus