Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice

J E Foreman; A Lionikas; D H Lang; J P Gyekis; M Krishnan; N A Sharkey; G S Gerhard; M.D. Grant; G P Vogler; H.A. Mack; J T Stout; J.W. Griffith; J M Lakoski; S M Hofer; G E McClearn; D J Vandenbergh; D A Blizard

doi:10.1111/j.1601-183X.2009.00516.x

Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice

J E Foreman, A Lionikas, D H Lang, J P Gyekis, M Krishnan, N A Sharkey, G S Gerhard, M.D. Grant, G P Vogler, H.A. Mack, J T Stout, J.W. Griffith, J M Lakoski, S M Hofer, G E McClearn, D J Vandenbergh, D A Blizard

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Abstract

A quantitative trait locus (QTL) analysis of behaviors across the life span was conducted in F(2) mice from a C57BL/6J x DBA/2J cross and 22 BXD recombinant inbred (RI) strains. Mice of three age groups were tested in a hole-board apparatus for 3 min on three occasions approximately 1 month apart (average age at test 150, 450 and 750 days, approximately 400 mice per group, divided equally by sex). Quantitative trait loci with small effect size were found on 11 chromosomes for hole-board activity (Hbact) and hole-board rearing (Hbrear). Analysis of 22 RI strains tested at 150 and 450 days of age found only suggestive linkage, with four QTL for Hbact overlapping with those from the F(2) analysis. There was a significant phenotypic correlation between Hbact and Hbrear (approximately 0.55-0.69) and substantial commonality among QTL for the two behaviors. QTL analyses of head-pokes (HP) and fecal boli (FB) only identified QTL at the suggestive level of significance. Age accounted for approximately 15% of the phenotypic variance (sex approximately 3%), and there were genotype by age interactions at approximately 25% of the Hbact and Hbrear QTL. Quantitative trait loci for Hbrear were relatively stable across the three measurement occasions (those for Hbact somewhat less so), although mean levels of each index declined markedly comparing the first to subsequent trials. Considered as a whole, the polygenic system influencing exploratory behaviors accounts for approximately the same amount of phenotypic variance as age (within the range studied), is stable across substantial periods of time, and acts, for the most part, independently of age and sex.

Original language	English
Pages (from-to)	714-727
Number of pages	14
Journal	Genes, Brain, and Behavior
Volume	8
Issue number	7
Early online date	23 Jun 2009
DOIs	https://doi.org/10.1111/j.1601-183X.2009.00516.x
Publication status	Published - Oct 2009

Keywords

age factors
aging
animals
behavior, animal
chromosome mapping
chromosomes, mammalian
crosses, genetic
DNA mutational analysis
epistasis, genetic
female
gene expression regulation, developmental
genetic variation
genotype
male
mice
mice, inbred C57BL
mice, inbred DBA
mice, inbred strains
motor skills
penetrance
phenotype
quantitative trait loci
sex factors
species specificity
time factors
squares
activity
life span
QTL
rears

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10.1111/j.1601-183X.2009.00516.x

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Foreman, J. E., Lionikas, A., Lang, D. H., Gyekis, J. P., Krishnan, M., Sharkey, N. A., Gerhard, G. S., Grant, M. D., Vogler, G. P., Mack, H. A., Stout, J. T., Griffith, J. W., Lakoski, J. M., Hofer, S. M., McClearn, G. E., Vandenbergh, D. J., & Blizard, D. A. (2009). Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice. Genes, Brain, and Behavior, 8(7), 714-727. https://doi.org/10.1111/j.1601-183X.2009.00516.x

Foreman, JE, Lionikas, A, Lang, DH, Gyekis, JP, Krishnan, M, Sharkey, NA, Gerhard, GS, Grant, MD, Vogler, GP, Mack, HA, Stout, JT, Griffith, JW, Lakoski, JM, Hofer, SM, McClearn, GE, Vandenbergh, DJ & Blizard, DA 2009, 'Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice', Genes, Brain, and Behavior, vol. 8, no. 7, pp. 714-727. https://doi.org/10.1111/j.1601-183X.2009.00516.x

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abstract = "A quantitative trait locus (QTL) analysis of behaviors across the life span was conducted in F(2) mice from a C57BL/6J x DBA/2J cross and 22 BXD recombinant inbred (RI) strains. Mice of three age groups were tested in a hole-board apparatus for 3 min on three occasions approximately 1 month apart (average age at test 150, 450 and 750 days, approximately 400 mice per group, divided equally by sex). Quantitative trait loci with small effect size were found on 11 chromosomes for hole-board activity (Hbact) and hole-board rearing (Hbrear). Analysis of 22 RI strains tested at 150 and 450 days of age found only suggestive linkage, with four QTL for Hbact overlapping with those from the F(2) analysis. There was a significant phenotypic correlation between Hbact and Hbrear (approximately 0.55-0.69) and substantial commonality among QTL for the two behaviors. QTL analyses of head-pokes (HP) and fecal boli (FB) only identified QTL at the suggestive level of significance. Age accounted for approximately 15% of the phenotypic variance (sex approximately 3%), and there were genotype by age interactions at approximately 25% of the Hbact and Hbrear QTL. Quantitative trait loci for Hbrear were relatively stable across the three measurement occasions (those for Hbact somewhat less so), although mean levels of each index declined markedly comparing the first to subsequent trials. Considered as a whole, the polygenic system influencing exploratory behaviors accounts for approximately the same amount of phenotypic variance as age (within the range studied), is stable across substantial periods of time, and acts, for the most part, independently of age and sex.",

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AU - Foreman, J E

AU - Lionikas, A

AU - Lang, D H

AU - Gyekis, J P

AU - Krishnan, M

AU - Sharkey, N A

AU - Gerhard, G S

AU - Grant, M.D.

AU - Vogler, G P

AU - Mack, H.A.

AU - Stout, J T

AU - Griffith, J.W.

AU - Lakoski, J M

AU - Hofer, S M

AU - McClearn, G E

AU - Vandenbergh, D J

AU - Blizard, D A

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AB - A quantitative trait locus (QTL) analysis of behaviors across the life span was conducted in F(2) mice from a C57BL/6J x DBA/2J cross and 22 BXD recombinant inbred (RI) strains. Mice of three age groups were tested in a hole-board apparatus for 3 min on three occasions approximately 1 month apart (average age at test 150, 450 and 750 days, approximately 400 mice per group, divided equally by sex). Quantitative trait loci with small effect size were found on 11 chromosomes for hole-board activity (Hbact) and hole-board rearing (Hbrear). Analysis of 22 RI strains tested at 150 and 450 days of age found only suggestive linkage, with four QTL for Hbact overlapping with those from the F(2) analysis. There was a significant phenotypic correlation between Hbact and Hbrear (approximately 0.55-0.69) and substantial commonality among QTL for the two behaviors. QTL analyses of head-pokes (HP) and fecal boli (FB) only identified QTL at the suggestive level of significance. Age accounted for approximately 15% of the phenotypic variance (sex approximately 3%), and there were genotype by age interactions at approximately 25% of the Hbact and Hbrear QTL. Quantitative trait loci for Hbrear were relatively stable across the three measurement occasions (those for Hbact somewhat less so), although mean levels of each index declined markedly comparing the first to subsequent trials. Considered as a whole, the polygenic system influencing exploratory behaviors accounts for approximately the same amount of phenotypic variance as age (within the range studied), is stable across substantial periods of time, and acts, for the most part, independently of age and sex.

KW - age factors

KW - aging

KW - animals

KW - behavior, animal

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KW - crosses, genetic

KW - DNA mutational analysis

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KW - female

KW - gene expression regulation, developmental

KW - genetic variation

KW - genotype

KW - male

KW - mice

KW - mice, inbred C57BL

KW - mice, inbred DBA

KW - mice, inbred strains

KW - motor skills

KW - penetrance

KW - phenotype

KW - quantitative trait loci

KW - sex factors

KW - species specificity

KW - time factors

KW - squares

KW - activity

KW - life span

KW - QTL

KW - rears

U2 - 10.1111/j.1601-183X.2009.00516.x

DO - 10.1111/j.1601-183X.2009.00516.x

M3 - Article

C2 - 19671078

VL - 8

SP - 714

EP - 727

JO - Genes, Brain, and Behavior

JF - Genes, Brain, and Behavior

SN - 1601-1848

IS - 7

ER -

Genetic architecture for hole-board behaviors across substantial time intervals in young, middle-aged and old mice

Abstract

Keywords

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