Subscribe to RSS
DOI: 10.1055/s-2005-861301
PNMT Transgenic Mice Have an Aggressive Phenotype
Publication History
Received 16 June 2004
Accepted after revision 7 October 2004
Publication Date:
12 April 2005 (online)
![](https://www.thieme-connect.de/media/hmr/200503/lookinside/thumbnails/10.1055-s-2005-861301-1.jpg)
Abstract
PNMT (phenylethanolamine-N-methyl-transferase) is the enzyme that catalyzes the formation of epinephrine from norepinephrine. In transgenic mice over-expressing PNMT, observations revealed a very high level of aggression compared to their background strain, C57BL/6J. To evaluate the influence of PNMT on aggression and emotionality in this transgenic line, single-sex male and female groups were independently established that consisted of either four wild-type mice or four transgenic mice overexpressing PNMT. The members of each group were littermates. Mixed single-sex groups consisting of two transgenic mice and two wild-type mice were also established. Almost no fights were observed within the female groups. In males, the transgenic line showed a significantly higher level of fighting than controls (p = 0.007) and mixed male groups (p = 0.02). Housing mice from the transgenic line in mixed groups with wild-type mice seems to decrease the level of aggression in the transgenic line. In conclusion, this is the first study to demonstrate a clear, significant increase in aggression arising from PNMT overexpression. This suggests an important role for central epinephrine levels in aggressive behavior.
Keywords
Epinephrine - Mice - Open field - Behavior - C57Bl/6
References
- 1 Snyder S H. Drugs and the brain. Scientific American Library New York; 1996
- 2 Haller J. Adrenomedullar Catecholamine Liberation and Carbohydrate-Metabolism During the 1St 30 Min of An Aggressive Encounter in Rats. Physiol Behav. 1993; 54 195-197
- 3 Haller J, Makara G, Kruk M R. Catecholaminergic involvement in the control of aggression: Hormones, the peripheral sympathetic, and central noradrenergic systems. Neurosci Biobehav R. 1998; 22 85-97
- 4 Mefford I N. Epinephrine in mammalian brain. Prog Neuro-psychoph. 1988; 12 365-388
-
5 Cooper J R, Bloom F E, Roth R T.
Norepinephrine and epinephrine. In: Cooper J, Bloom FE, and Roth R (eds) The biochemical basis of neuropharmacology. Oxford University Press Oxford; 1996: 226-292 - 6 Haller J, Makara G B, Kruk M R. Catecholaminergic involvement in the control of aggression: Hormones, the peripheral sympathetic, and central noradrenergic systems. Neurosci Biobehav R. 1998; 22 85-97
- 7 Böttner A, Haidan A, Eisenhofer G, Kristensen K, Castle A L, Scherbaum W A, Schneider H, Chrousos G P, Bornstein S R. Increased body fat mass and suppression of circulating leptin levels in response to hypersecretion of epinephrine in phenylethanolamine-N-methyltransferase (PNMT)-overexpressing mice. Endocrinology. 2000; 141 4239-4246
- 8 Nicklas W, Baneux P, Boot R, Decelle T, Deeny AA, Fumanelli M, Illgen-Wilcke B. Recommendations for the health monitoring of rodent and rabbit colonies in breeding and experimental units. Lab Anim. 2002; 36 20-42
- 9 Hurst J L, Fang J, Barnard C J. The role of substrate odours in maintaining social tolerance between male house mice, Mus musculus domesticus. Anim Behav. 1993; 45 997-1006
- 10 Hurst J L, Fang J, Barnard C. The role of substrate odours in maintaining social tolerance between male house mice, Mus musculus domesticus: relatedness, incidental kinship effects and the establishment of social status. Anim Behav. 1994; 48 157-167
- 11 Gray S J, Hurst J L. The effects of cage cleaning on aggression within groups of male laboratory mice. Anim Behav. 1995; 49 821-826
- 12 Jennings M, Batchelor G R, Brain P F, Dick A, Elliott H, Francis R J, Hubrecht R C, Hurst J L, Morton D B, Peters A G, Raymond R, Sales G D, Sherwin C M, West C D. Refining rodent husbandry: The mouse. Lab Anim. 1998; 32 233-259
- 13 Van Loo P LP, Kruitwagen C LJJ, Van Zutphen L FM, Koolhaas J M, Baumans V. Modulation of aggression in male mice: Influence of cage cleaning regime and scent marks. Anim Welfare. 2000; 9 281-295
- 14 Eisenhofer G, Goldstein D S, Stull R, Keiser H R, Sunderland T, Murphy D L, Kopin I J. Simultaneous liquid-chromatographic determination of 3,4-dihydroxyphenylglycol, catecholamines, and 3,4-dihydroxyphenylalanine in plasma, and their responses to inhibition of monoamine oxidase. Clinical Chemistry. 1986; 32 2030-2033
- 15 Latham N, Mason G. From house mouse to mouse house: the behavioural biology of free-living Mus musculus and its implications in the laboratory. Appl Anim Behav Sci. 2004; 86 261-289
- 16 Latham N, Mason G. From house mouse to mouse house: the behavioural biology of free-living Mus musculus and its implications in the laboratory. Appl Anim Behav Sci. 2004; 86 261-289
- 17 Haemisch A, Voss T, Gärtner K. Effects of environmental enrichment on aggressive behaviour, dominance hierarchies, and endocrine states in male DBA/2J mice. Physiol Behav. 1994; 56 1041-1048
- 18 Ely D L, Henry J P. Neuroendocrine response patterns in dominant and subordinate mice. Horm Behav. 1978; 10 156-169
- 19 Maengwyn-Davies G D, Johnson D G, Thoa N B, Weise V K, Kopin I J. Influence of isolation and of fighting on adrenal Tyrosine hydroxylase and Phenylethanolamine-N-Methyltransferase activities in three strains of mice. Psychopharmacologia. 1973; 28 339-350
- 20 Hucklebridge F H, Gamal-El-Din L, Brain P F. Social status and the adrenal medulla in the house mouse (Mus musculus, L.). Behav Neural Biol. 1981; 33 345-363
- 21 Haemisch A, Gärtner K. Dissociation between adrenal tyrosinehydroxylase and phenylethanolamine N-methyltransferase activities following repeated experience of defeats in individually housed male DBA/2J mice. Physiol Behav. 1996; 59 1117-1122
- 22 Butler R G. Population size, social behaviour, and dispersal in house mice: A quantitative investigation. Anim Behav. 1980; 28 78-85
- 23 Cases O, Seif I, Grimsby J, Gaspar P, Chen K, Pournin S, Müller U, Aguet M, Babinet C, Chen S hih , De Maeyer E. Aggressive behavior and altered amounts of brain serotonin and norepinephrine in mice lacking MAOA. Science. 1995; 268 1763-1766
- 24 Abelson J L, Weg J G, Nesse R M, Curtis G C. Neuroendocrine responses to laboratory panic: Cognitive intervention in the doxapram model. Psychoneuroendocrinology. 1996; 21 375-390
-
25 Cooper J, Bloom F E, Roth R T.
Serotonin (5-hydroxytryptamine) and histamine. In: Cooper J, Bloom FE, Roth RT (Eds) The biochemical basis of neuropharmacology. Oxford University Press Oxford; 1996: 352-409 - 26 Nelson R J, Chiavegatto S. Molecular basis of aggression. Trends Neurosci. 2001; 24 713-719
- 27 Miczek K A, Maxson S C, Fish E W, Faccidomo S. Aggressive behavioral phenotypes in mice. Behav Brain Res. 2001; 125 167-181
Dorte Bratbo Sørensen
The Royal Veterinary and Agricultural University of Copenhagen · Division of Laboratory Animal Science and Welfare · Department of Veterinary Pathobiology
Groennegaardsvej 15 · 1870 Frederiksberg C · Denmark
Phone: +45 35 28 27 24
Fax: +45 35 28 30 22
Email: dobj@kvl.dk