Behavior Genetics

, Volume 40, Issue 2, pp 201–210 | Cite as

Differences in Aggressive Behavior and DNA Copy Number Variants Between BALB/cJ and BALB/cByJ Substrains

  • Lady Velez
  • Greta Sokoloff
  • Klaus A. Miczek
  • Abraham A. Palmer
  • Stephanie C. Dulawa
Original Research

Abstract

Some BALB/c substrains exhibit different levels of aggression. We compared aggression levels between male BALB/cJ and BALB/cByJ substrains using the resident intruder paradigm. These substrains were also assessed in other tests of emotionality and information processing including the open field, forced swim, fear conditioning, and prepulse inhibition tests. We also evaluated single nucleotide polymorphisms (SNPs) previously reported between these BALB/c substrains. Finally, we compared BALB/cJ and BALB/cByJ mice for genomic deletions or duplications, collectively termed copy number variants (CNVs), to identify candidate genes that might underlie the observed behavioral differences. BALB/cJ mice showed substantially higher aggression levels than BALB/cByJ mice; however, only minor differences in other behaviors were observed. None of the previously reported SNPs were verified. Eleven CNV regions were identified between the two BALB/c substrains. Our findings identify a robust difference in aggressive behavior between BALB/cJ and BALB/cByJ substrains, which could be the result of the identified CNVs.

Keywords

Aggression Resident intruder BALB/c CNV Substrain 

Notes

Acknowledgments

This work was supported by National Institutes of Health grants K01MH071555 and R01MH079424, and Brain Research Foundation and NARSAD Awards to S.C.D.

Disclosure/Conflict of interest

None of the authors reported biomedical financial interests or potential conflicts of interest.

References

  1. Blanchard RJ, Wall PM, Blanchard DC (2003) Problems in the study of rodent aggression. Horm Behav 44:161–170CrossRefPubMedGoogle Scholar
  2. Brain P (1975) What does individual housing mean to a mouse? Life Sci 16:187–200CrossRefPubMedGoogle Scholar
  3. Ciaranello RD, Lipsky A, Axelrod J (1974) Association between fighting behavior and catecholamine biosynthetic enzyme activity in two inbred mouse sublines. Proc Natl Acad Sci USA 71:3006–3008CrossRefPubMedGoogle Scholar
  4. Crawley JN, Schleidt WM, Contrera JF (1975) Does social environment decrease propensity to fight in male mice? Behav Biol 15:73–83CrossRefPubMedGoogle Scholar
  5. Cryan JF, Page ME, Lucki I (2002) Noradrenergic lesions differentially alter the antidepressant-like effects of reboxetine in a modified forced swim test. Eur J Pharmacol 436(3):197–205Google Scholar
  6. D’Adamo P, Welzl H, Papadimitriou S, Raffaele di Barletta M, Tiveron C, Tatangelo L, Pozzi L, Chapman PF et al (2002) Deletion of the mental retardation gene Gdi1 impairs associative memory and alters social behavior in mice. Hum Mol Genet 11:2567–2580CrossRefPubMedGoogle Scholar
  7. Egan CM, Sridhar S, Wigler M, Hall IM (2007) Recurrent DNA copy number variation in the laboratory mouse. Nat Genet 39:1384–1389CrossRefPubMedGoogle Scholar
  8. Else T, Hammer GD (2005) Genetic analysis of adrenal absence: agenesis and aplasia. Trends Endocrinol Metab 16:458–468CrossRefPubMedGoogle Scholar
  9. Frints SG, Marynen P, Hartmann D, Fryns JP, Steyaert J, Schachner M, Rolf B, Craessaerts K et al (2003) CALL interrupted in a patient with non-specific mental retardation: gene dosage-dependent alteration of murine brain development and behavior. Hum Mol Genet 12:1463–1474CrossRefPubMedGoogle Scholar
  10. Geyer MA, Dulawa SC (2004) Current protocols in neuroscience. In: Crawley J, Skolnick P (eds) Assessment of murine startle response, prepulse inhibition, and habituation. John Wiley & Sons, New YorkGoogle Scholar
  11. Hishimoto A, Liu QR, Drgon T, Pletnikova O, Walther D, Zhu XG, Troncoso JC, Uhl GR (2007) Neurexin 3 polymorphisms are associated with alcohol dependence and altered expression of specific isoforms. Hum Mol Genet 16:2880–2891CrossRefPubMedGoogle Scholar
  12. Kelai S, Maussion G, Noble F, Boni C, Ramoz N, Moalic JM, Peuchmaur M, Gorwood P et al (2008) Nrxn3 upregulation in the globus pallidus of mice developing cocaine addiction. Neuroreport 19:751–755CrossRefPubMedGoogle Scholar
  13. Kume T, Deng K, Hogan BL (2000) Minimal phenotype of mice homozygous for a null mutation in the forkhead/winged helix gene, Mf2. Mol Cell Biol 20:1419–1425CrossRefPubMedGoogle Scholar
  14. Les EP (1990) A brief history of the two substrains of BALB/c, BALB/cJ, and BALB/cByJ available from animal resources. JAX notes, 443Google Scholar
  15. Maengwyn-Davies GD, Johnson DG, Thoa NB, Weise VK, Kopin IJ (1973) Influence of isolation and of fighting on adrenal tyrosine hydroxylase and phenylethanolamine-N-methyltransferase activities in three strains of mice. Psychopharmacologia 28:339–350CrossRefPubMedGoogle Scholar
  16. Mansbach RS, Geyer MA, Braff DL (1988) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology (Berl) 94:507–514CrossRefGoogle Scholar
  17. Miczek KA, O’Donnell JM (1978) Intruder-evoked aggression in isolated and nonisolated mice: effects of psychomotor stimulants and L-dopa. Psychopharmacology (Berl) 57:47–55CrossRefGoogle Scholar
  18. Miczek KA, Maxson SC, Fish EW, Faccidomo S (2001) Aggressive behavioral phenotypes in mice. Behav Brain Res 125:167–181CrossRefPubMedGoogle Scholar
  19. Olivier B, Mos J (1992) Rodent models of aggressive behavior and serotonergic drugs. Prog Neuropsychopharmacol Biol Psychiatry 16:847–870CrossRefPubMedGoogle Scholar
  20. Petkov PM, Ding Y, Cassell MA, Zhang W, Wagner G, Sargent EE, Asquith S, Crew V et al (2004) An efficient SNP system for mouse genome scanning and elucidating strain relationships. Genome Res 14:1806–1811CrossRefPubMedGoogle Scholar
  21. Ponder CA, Kliethermes CL, Drew MR, Muller J, Das K, Risbrough VB, Crabbe JC, Gilliam TC et al (2007) Selection for contextual fear conditioning affects anxiety-like behaviors and gene expression. Genes Brain Behav 6:736–749CrossRefPubMedGoogle Scholar
  22. Rodd ZA, Kimpel MW, Edenberg HJ, Bell RL, Strother WN, McClintick JN, Carr LG, Liang T et al (2008) Differential gene expression in the nucleus accumbens with ethanol self-administration in inbred alcohol-preferring rats. Pharmacol Biochem Behav 89:481–498CrossRefPubMedGoogle Scholar
  23. Shanahan NA, Holick Pierz KA, Masten VL, Waeber C, Ansorge M, Gingrich JA, Geyer MA, Hen R, Dulawa SC (2009) Chronic reductions in serotonin transporter function prevent 5-HT1B-induced behavioral effects in mice. Biol Psychiatry 65(5):401–408Google Scholar
  24. Tarpey PS, Raymond FL, Nguyen LS, Rodriguez J, Hackett A, Vandeleur L, Smith R, Shoubridge C et al (2007) Mutations in UPF3B, a member of the nonsense-mediated mRNA decay complex, cause syndromic and nonsyndromic mental retardation. Nat Genet 39:1127–1133CrossRefPubMedGoogle Scholar
  25. Watkins-Chow DE, Pavan WJ (2008) Genomic copy number and expression variation within the C57BL/6J inbred mouse strain. Genome Res 18:60–66CrossRefPubMedGoogle Scholar
  26. Williams R, Lim JE, Harr B, Wing C, Walters R, Distler G, Teschke M, Wu C et al (2009) A common and unstable copy number variant is associated with differences in Glo1 expression and anxiety-like behavior. Plos One (in press)Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Lady Velez
    • 1
  • Greta Sokoloff
    • 2
  • Klaus A. Miczek
    • 3
  • Abraham A. Palmer
    • 1
    • 2
  • Stephanie C. Dulawa
    • 1
  1. 1.Department of Psychiatry and Behavioral NeuroscienceUniversity of ChicagoChicagoUSA
  2. 2.Department of Human GeneticsUniversity of ChicagoChicagoUSA
  3. 3.Departments of Psychology, Psychiatry, Pharmacology and NeuroscienceTufts UniversityMedfordUSA

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