Behavioral phenotyping of Kaiso-deficient mice. V. S. Korostina, A. V. Kulikov

Abstract:

Kaiso is a methyl DNA-binding protein, which participates in the epigenetic regulation of gene expression. It binds methylated DNA with its zinc-finger domain and recruits repressive protein complexes to the methylated DNA fragments by the interaction of the BTB/POZ domain with the complex of NCoR corepressor and histone deacetylase, thereby performing transcription repression. A Kaiso-deficient mouse strain (KO) with the C57BL/6 strain background has been bred. Here we compare the behavior of KO mice and wild-type control C57BL/6 mice (WT) in the classic battery of behavioral tests, including the open field, elevated plus maze, and forced swim tests. We have shown that knockout of the Kaiso gene increases the locomotory and exploratory activities of KO mice in the open field test. Kaiso-deficient mice spend more time in the center of the open field than WT mice. No effect of Kaiso gene knockout on anxietyrelated behavior has been observed in the elevated plus-maze. However, Kaiso gene deficiency produces a pronounced antidepressant-like effect in the forced swim test: Unlike WT mice, KO mice do not show any depressive-like freezing in this test. These results are the first piece of experimental evidence for the involvement of Kaiso protein in the regulation of brain functioning and beha­vior. The Kaiso-deficient strain is a new and promising model of the genetic, molecular, and neuronal mechanisms mediating the epigenetic regulation of brain functions and behavior.

About The Authors:

V. S. Korostina. Institute of Bioengineering, Research Center of Biotechnology of the Russian Academy of Sciences, Russian Federation, Moscow

A. V. Kulikov. Institute of Cytology and Genetics SB RAS; Novosibirsk State University, Russian Federation, Novosibirsk

References:

1. Bali P., Im H.I., Kenny P.J. Methylation, memory and addiction. Epigenetics. 2011;6: 671-674.

2. Belzung C., Griebel G. Measuring normal and pathological anxiety-like behavior in mice: a review. Behav. Brain Res. 2001;125: 141-149.

3. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16:6-21.

4. Crawley J.N. Behavioral phenotyping strategies for mutant mice. Neuron. 2008;57:809-818.

5. Cryan J.F., Mombereau C. In search of a depressive mouse: utility of models for studying depression-related behavior in genetically modified mice. Mol. Psychiatry. 2004;9:326-357.

6. Daniel J.M., Reynolds A.B. The catenin p-120 (ctn) interacts with Kaiso, a novel BTB/POZ domain zinc finger transcription factor. Mol. Cell. Biol. 1999;19:3614-3623.

7. Daniel J.M. Dancing in and out of the nucleus: p120ctn and the transcription factor Kaiso. Biochim. Biophys. Acta. 2007;1772:59-68.

8. Della Ragione F., Tiunova A., Vacca M., Strazzullo M., Gonzalezm E., Armstrong J., Valero R., Campanile C., Pineda M., Hulten M., Monros E., D’Esposito M., Prokhortchouk E. The X-linked methyl binding protein gene Kaiso is highly expressed in brain but is not mutated in Rett syndrome patients. Gene. 2006;373:83-89.

9. Denenberg V.H. Open-field behavior in the rat: What does it mean? Ann. N.Y. Acad. Sci. 1969;159:852-859.

10. Filion G.J., Zhenilo S., Salozhin S., Yamada D., Prokhortchouk E., Defossez P.A. A family of human zinc finger proteins that bind methylated DNA and repress transcription. Mol. Cell. Biol. 2006;26:169-181.

11. Fun G., Hutnick L. Methyl-CpG binding proteins in the nervous system. Cell Res. 2005;15:255-261.

12. Hendrich B., Guy J., Ramsahoye B., Wilson V.A., Bird A. Closely related proteins MBD2 and MBD3 play distinctive but interacting roles in mouse development. Genes Dev. 2001;15:710-723.

13. Klose R.J., Bird A.P. Genomic DNA methylation: the mark and its mediators. Trends Biochem. Sci. 2006;31:89-97.

14. Kulikov A.V., Morozova M.V., Kulikov V.A., Kirichuk V.S., Popova N.K. Automated analysis of antidepressants’ effect on the forced swim test. J. Neurosci. Meth. 2010;191:26-31.

15. Kulikov A.V., Tikhonova M.A., Kulikov V.A. Automated measurement of special preference in the open field test with transmitted lighting. J. Neurosci. Meth. 2008;170:345-351.

16. Kulikov A.V., Tikhonova M.A., Kulikova E.A., Volcho K.P., Khomenko T.M., Salakhutdinov N.F., Popova N.K. Antidepressant activity of 8-(trifluoromethyl)-1,2,3,4,5-benzopentathiepin-6-amine hydrochloride (TC-2153): Comparison with classical antidepressants. Lett. Drug Design Discov. 2014;11:169-173.

17. Lopes E.C., Valls E., Figueroa M.E., Mazur A., Meng F.G., Chiosis G., Laird P.W., Schreiber-Agus N., Greally J.M., Prokhortchouk E., Melnick A. Kaiso contributes to DNA methylation-dependent silencing of tumor suppressor genes in colon cancer cell lines. Cancer Res. 2008;68:7258-7263.

18. Lubin F.D., Gupta S., Parrish R.R., Grissom N.M., Davis R.L. Epigenetic mechanisms: critical contributors to long-term memory formation. Neuroscientist. 2011;17:616-632.

19. Milner L.C., Crabbe J.C. Three murine anxiety models: results from multiple inbred strain comparison. Genes Brain Behav. 2008;7:496-505.

20. Pellow S., Chopin P., File S.E., Briley M. Validation of open:closed arm entries in an elevated plus-maze as a measure of anxiety in the rat. J. Neurosci. Meth. 1985;14:149-167.

21. Porsolt R.D., Le Pichon M., Jalfre M. Depression: a new animal model sensitive to antidepressant treatments. Nature. 1977;266:730-732.

22. Prokhortchouk A., Sansom O., Selfridge J., Caballero I.M., Salozhin S., Aithozhina D., Cerchietti L., Meng F.G., Augenlicht L.H., Mariadason J.M., Hendrich B., Melnick A., Prokhortchouk E., Clarke A., Bird A. Kaiso-deficient mice show resistance to intestinal cancer. Mol. Cell Biol. 2006;26:199-208.

23. Prut L., Belzung C. The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review. Eur. J. Pharmacol. 2003;463:3-33.

24. Roux J.C., Villard L. Biogenic amines in Rett syndrome: the usual suspects. Behav. Genet. 2010;40:59-75.

25. Shumskaya V.S., Zhigalova N.A., Prokhorchouk A.V., Prokhorchouk E.B. Distribution of Kaiso protein in mouse tissues. Histochem. Cell Biol. 2015;143:29-43.

26. Standford C. The open field test: reinventing the weel. J. Psychopharmacol. 2007;21:134-135.

27. Tecott L.H. The genes and brain of mice and men. Am. J. Psychiatry. 2003;160:646-656.

28. Tropea D., Giacometti E., Wilson N.R., Beard C., McCurry C., Fu D.D., Flannery R., Jaenisch R., Sur M. Partial reversal of Rett syndromelike symptoms in MeCP2 mutant mice. Proc. Natl Acad. Sci. USA. 2009;106:2029-2034.

29. Wade P.A. Methyl CpG-binding proteins and transcriptional repression. Bioessays. 2001;23:1131-1137.

30. Wahlsten D., Rustay N.R., Metten P., Crabbe J.C. In search of a better mouse test. Trends Neurosci. 2003;26:132-136.

31. Willner P. Animal models of depression: an overview. Pharmacol. Ther. 1990;45:425-455.

32. Willner P., Mitchell P.J. The validity of animal models of predisposition to depression. Behav. Pharmacol. 2002;13:169-188.

33. Yoon H.G., Chan D.W., Reynolds A.B., Qin J., Wong J. N-CoR mediates DNA methylation-dependent repression through a methyl CpG binding protein Kaiso. Mol. Cell. 2003;12:723-734.

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