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Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposon in Eutherians.

Irie M, Yoshikawa M, Ono R, Iwafune H, Furuse T, Yamada I, Wakana S, Yamashita Y, Abe T, Ishino F, Kaneko-Ishino T - PLoS Genet. (2015)

Bottom Line: Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein.Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice.Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences, Tokai University, Isehara, Kanagawa, Japan; Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.

ABSTRACT
Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16) causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

No MeSH data available.


Related in: MedlinePlus

Abnormal behavior in the Sirh11/Zcchc16 KO mice.(A) Light/Dark transition test. The left panel shows the latency time before entering into the light chamber. The right panel shows the number of transitions. The white and black bars represent WT and KO, respectively. Each data point represents the mean ± S. E. M. (N = 7 each). The asterisks indicate significant differences between the male WT and KO mice (*: p < 0.05). (B) Home-cage activity test. Upper: The plots show the activity counts every hour over 5 days. The white and grey areas indicate the light and dark phases, respectively. Middle: The white and black bars represent the activity counts in the WT and KO, respectively (mean ± S. D. (N = 7 each)). Zeitgeiber time (ZT) is shown on the x-axis. The asterisks indicate significant differences between the male WT and KO mice (**: p < 0.01, *: p < 0.05). Lower: the table shows the p-values of the two-way ANOVA at each ZT. The yellow columns indicate a significant difference in genotype (p < 0.05). (C) Y-maze test. Left: each plot shows the percentage of alternation behavior. Right: each plot shows the number of total arm entries. The white and black plots represent the WT and KO, respectively. The asterisk indicates a significant difference between the male WT (N = 6) and KO (N = 8) mice (*: p < 0.05).
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pgen.1005521.g003: Abnormal behavior in the Sirh11/Zcchc16 KO mice.(A) Light/Dark transition test. The left panel shows the latency time before entering into the light chamber. The right panel shows the number of transitions. The white and black bars represent WT and KO, respectively. Each data point represents the mean ± S. E. M. (N = 7 each). The asterisks indicate significant differences between the male WT and KO mice (*: p < 0.05). (B) Home-cage activity test. Upper: The plots show the activity counts every hour over 5 days. The white and grey areas indicate the light and dark phases, respectively. Middle: The white and black bars represent the activity counts in the WT and KO, respectively (mean ± S. D. (N = 7 each)). Zeitgeiber time (ZT) is shown on the x-axis. The asterisks indicate significant differences between the male WT and KO mice (**: p < 0.01, *: p < 0.05). Lower: the table shows the p-values of the two-way ANOVA at each ZT. The yellow columns indicate a significant difference in genotype (p < 0.05). (C) Y-maze test. Left: each plot shows the percentage of alternation behavior. Right: each plot shows the number of total arm entries. The white and black plots represent the WT and KO, respectively. The asterisk indicates a significant difference between the male WT (N = 6) and KO (N = 8) mice (*: p < 0.05).

Mentions: Although no evident structural abnormalities were found in the KO mouse brain (S4 Fig), it was noticed that abnormal behaviors were exhibited. For example, they displayed agitated movement in their cages when staff personnel entered the breeding room, and sometimes jumped out when their cages were exchanged. Therefore, comprehensive behavior tests were carried out using 8–10 w males. Sirh11/Zcchc16 KO mice exhibited no abnormality in the open field test (9 and 10 w), but in the Light/Dark transition test (8 w) the latency before entering into the light chamber was significantly decreased (unpaired two sample t-test, t(12) = 2.52, p = 0.0269), while the number of transitions was significantly increased (unpaired two sample t-test, t(12) = -2.58, p = 0.0242) compared to the wild type (WT), suggesting a reduced attention and/or enhanced impulsivity (Fig 3A). They also exhibited significantly higher activity during the dark period of the home-cage activity test (10 w), especially just after the “light to dark (Zeitgeiber time (ZT) 12 and 13)” (effect of genotype, F(1, 60) = 7.86, p = 0.00681 and effect of genotype, F(1, 60) = 5.35, p = 0.0241, respectively) as well as just before the “dark to light (ZT23)” (F(1, 60) = 9.77, p = 0.00274) transition periods. There was also lower activity at ZT19 (F(1, 60) = 7.56), p = 0.00788), while there was no significant difference in the light periods (ZT0-ZT11), suggesting hyperactivity, especially when the light conditions are changed or about to be changed (Fig 3B).


Cognitive Function Related to the Sirh11/Zcchc16 Gene Acquired from an LTR Retrotransposon in Eutherians.

Irie M, Yoshikawa M, Ono R, Iwafune H, Furuse T, Yamada I, Wakana S, Yamashita Y, Abe T, Ishino F, Kaneko-Ishino T - PLoS Genet. (2015)

Abnormal behavior in the Sirh11/Zcchc16 KO mice.(A) Light/Dark transition test. The left panel shows the latency time before entering into the light chamber. The right panel shows the number of transitions. The white and black bars represent WT and KO, respectively. Each data point represents the mean ± S. E. M. (N = 7 each). The asterisks indicate significant differences between the male WT and KO mice (*: p < 0.05). (B) Home-cage activity test. Upper: The plots show the activity counts every hour over 5 days. The white and grey areas indicate the light and dark phases, respectively. Middle: The white and black bars represent the activity counts in the WT and KO, respectively (mean ± S. D. (N = 7 each)). Zeitgeiber time (ZT) is shown on the x-axis. The asterisks indicate significant differences between the male WT and KO mice (**: p < 0.01, *: p < 0.05). Lower: the table shows the p-values of the two-way ANOVA at each ZT. The yellow columns indicate a significant difference in genotype (p < 0.05). (C) Y-maze test. Left: each plot shows the percentage of alternation behavior. Right: each plot shows the number of total arm entries. The white and black plots represent the WT and KO, respectively. The asterisk indicates a significant difference between the male WT (N = 6) and KO (N = 8) mice (*: p < 0.05).
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4581854&req=5

pgen.1005521.g003: Abnormal behavior in the Sirh11/Zcchc16 KO mice.(A) Light/Dark transition test. The left panel shows the latency time before entering into the light chamber. The right panel shows the number of transitions. The white and black bars represent WT and KO, respectively. Each data point represents the mean ± S. E. M. (N = 7 each). The asterisks indicate significant differences between the male WT and KO mice (*: p < 0.05). (B) Home-cage activity test. Upper: The plots show the activity counts every hour over 5 days. The white and grey areas indicate the light and dark phases, respectively. Middle: The white and black bars represent the activity counts in the WT and KO, respectively (mean ± S. D. (N = 7 each)). Zeitgeiber time (ZT) is shown on the x-axis. The asterisks indicate significant differences between the male WT and KO mice (**: p < 0.01, *: p < 0.05). Lower: the table shows the p-values of the two-way ANOVA at each ZT. The yellow columns indicate a significant difference in genotype (p < 0.05). (C) Y-maze test. Left: each plot shows the percentage of alternation behavior. Right: each plot shows the number of total arm entries. The white and black plots represent the WT and KO, respectively. The asterisk indicates a significant difference between the male WT (N = 6) and KO (N = 8) mice (*: p < 0.05).
Mentions: Although no evident structural abnormalities were found in the KO mouse brain (S4 Fig), it was noticed that abnormal behaviors were exhibited. For example, they displayed agitated movement in their cages when staff personnel entered the breeding room, and sometimes jumped out when their cages were exchanged. Therefore, comprehensive behavior tests were carried out using 8–10 w males. Sirh11/Zcchc16 KO mice exhibited no abnormality in the open field test (9 and 10 w), but in the Light/Dark transition test (8 w) the latency before entering into the light chamber was significantly decreased (unpaired two sample t-test, t(12) = 2.52, p = 0.0269), while the number of transitions was significantly increased (unpaired two sample t-test, t(12) = -2.58, p = 0.0242) compared to the wild type (WT), suggesting a reduced attention and/or enhanced impulsivity (Fig 3A). They also exhibited significantly higher activity during the dark period of the home-cage activity test (10 w), especially just after the “light to dark (Zeitgeiber time (ZT) 12 and 13)” (effect of genotype, F(1, 60) = 7.86, p = 0.00681 and effect of genotype, F(1, 60) = 5.35, p = 0.0241, respectively) as well as just before the “dark to light (ZT23)” (F(1, 60) = 9.77, p = 0.00274) transition periods. There was also lower activity at ZT19 (F(1, 60) = 7.56), p = 0.00788), while there was no significant difference in the light periods (ZT0-ZT11), suggesting hyperactivity, especially when the light conditions are changed or about to be changed (Fig 3B).

Bottom Line: Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein.Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice.Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

View Article: PubMed Central - PubMed

Affiliation: School of Health Sciences, Tokai University, Isehara, Kanagawa, Japan; Department of Epigenetics, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Bunkyo-ku, Tokyo, Japan.

ABSTRACT
Gene targeting of mouse Sushi-ichi-related retrotransposon homologue 11/Zinc finger CCHC domain-containing 16 (Sirh11/Zcchc16) causes abnormal behaviors related to cognition, including attention, impulsivity and working memory. Sirh11/Zcchc16 encodes a CCHC type of zinc-finger protein that exhibits high homology to an LTR retrotransposon Gag protein. Upon microdialysis analysis of the prefrontal cortex region, the recovery rate of noradrenaline (NA) was reduced compared with dopamine (DA) after perfusion of high potassium-containing artificial cerebrospinal fluid in knockout (KO) mice. These data indicate that Sirh11/Zcchc16 is involved in cognitive function in the brain, possibly via the noradrenergic system, in the contemporary mouse developmental systems. Interestingly, it is highly conserved in three out of the four major groups of the eutherians, euarchontoglires, laurasiatheria and afrotheria, but is heavily mutated in xenarthran species such as the sloth and armadillo, suggesting that it has contributed to brain evolution in the three major eutherian lineages, including humans and mice. Sirh11/Zcchc16 is the first SIRH gene to be involved in brain function, instead of just the placenta, as seen in the case of Peg10, Peg11/Rtl1 and Sirh7/Ldoc1.

No MeSH data available.


Related in: MedlinePlus