A third component causing random variability beside environment and genotype. A reason for the limited success of a 30 year long effort to standardize laboratory animals?
Abstract
This paper is a review of experiments, performed in our laboratory during the past 20 years, designed to analyse the significance of different components of random variability in quantitative traits in laboratory rats and mice. Reduction of genetic variability by using inbred strains and reduction of environmental variability by highly standardized husbandry in laboratory animals did not remarkably reduce the range of random variability in quantitative biological traits. Neither did a tremendous increase of the environmental variability (i.e., living in a natural setting) increase it. Therefore, the postnatal environment cannot be that important as the source of random variability. Utilizing methods established in twin research, only 20–30% of the range of the body weight in inbred mice were directly estimated to be of environmental origin. The remaining 70–80% were due to a third component creating biological random variability, in addition to the genetic and environmental influences. This third component is effective at or before fertilization and may originate from ooplasmic differences. It is the most important component of the phenotypic random variability, fixing its range and dominating the genetic and the environmental component. The Gaussian distribution of the body weights observed, even in inbred animals, seems to be an arrangement supporting natural selection rather than the consequence of heterogeneous environmental influences. In a group of inbred rats, the males with the highest chance of parenting the next generation were gathered in the central classes of the distribution of the body weight.
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Inbred laboratory mice raised in standardized conditions display high phenotypic trait variability and are prone to polyphenism.
“Inbred laboratory mice raised in standardized conditions nevertheless keep displaying high phenotypic trait variability (Gartner, 1990; Tuttle et al, 2018) and are prone to polyphenism, that is, several discrete phenotypes on the same genetic background (Dalgaard et al, 2016; Yang et al, 2022).”
From An extended transcription factor regulatory network controls hepatocyte identity (2023) · cites this paper as Gartner, 1990
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Tikhodeyev, O. N., & Shcherbakova, O. (2019) · Behavior Genetics · doi:10.1007/s10519-019-09950-1 · Cited by 40 · see citing works
Graham, J. H. (2021) · Symmetry · doi:10.3390/sym13071204 · Cited by 51 · see citing works
“Thus, 90 years later, Gärtner [6] reached precisely the same, and surprising to him, conclusion when he tried to produce uniform lines of laboratory rats and mice by repeatedly inbreeding them.”
BackgroundWhite, T. J. H. (2019) · Journal of the American Academy of Child & Adolescent Psychiatry · doi:10.1016/j.jaac.2019.02.010 · Cited by 33 · see citing works
Wahlsten, D., Crabbe, J., & Dudek, B. (2001) · Behavioural Brain Research · doi:10.1016/s0166-4328(01)00283-2 · Cited by 33 · see citing works
“Strenuous attempts to render the laboratory environment perfectly uniform in order to expunge individual differences among genetically identical, inbred mice, have met with failure even for anatomical and physiological phenotypes [13].”
Specification of hepatopancreas progenitors in zebrafish by hnf1ba and wnt2bb
Lancman, J. J., Zvenigorodsky, N., Gates, K. P., Zhang, D.-H., Solomon, K. S., Humphrey, R. K., Kuo, T., Setiawan, L., Verkade, H., Chi, Y.-I., et al. (2013) · Development · doi:10.1242/dev.090993 · Cited by 32 · see citing works
“…heterozygous HNF1B mutations in individuals with MODY5 result in a reduction of HNF1B function to a crucial threshold that is sensitive to stochastic developmental variation (Gärtner, 1990; Baranzini et al., 2010; Raj et al., 2010), which can be sensitive to variations in genetic background.”
BackgroundMaternal Prenatal Nutrition and Health in Grandchildren and Subsequent Generations
Susser, E., Kirkbride, J. B., Heijmans, B. T., Kresovich, J. K., Lumey, L. H., & Stein, A. D. (2010) · Annual Review of Anthropology · doi:10.1146/annurev-anthro-081309-145645 · Cited by 31 · see citing works
Alter, M. D., Rubin, D. B., Ramsey, K. M., Halpern, R., Stephan, D. A., Abbott, L. F., & Hen, R. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003344 · Cited by 29 · see citing works
“Monozygotic twin mice (genetically identical mice that are generated from a single zygote by dividing the blastocyst at the 8-cell stage to produce 2 viable embryos) are significantly more alike for multiple complex traits than are dizygotic twin mice (genetically identical mice obtained from different zygotes) [5].”
BackgroundGenetically alike Syrian hamsters display both bifoliate and trifoliate aortic valves
Sans-Coma, V., Fernández, M. C., Fernández, B., Durán, A. C., Anderson, R., & Arqué, J. (2012) · Journal of Anatomy · doi:10.1111/j.1469-7580.2011.01440.x · Cited by 31 · see citing works
“The phenotype results from the interaction between genotype and environmental factors, along with an additional third component (Gärtner, 1990) of stochastic nature that causes random variation.”
BackgroundNaturally clonal vertebrates are an untapped resource in ecology and evolution research
Laskowski, K., Doran, C., Bierbach, D., Krause, J., & Wolf, M. (2019) · Nature Ecology & Evolution · doi:10.1038/s41559-018-0775-0 · Cited by 29 · see citing works
Blewitt, M. E., Chong, S., & Whitelaw, E. (2004) · Trends in Genetics · doi:10.1016/j.tig.2004.08.011 · Cited by 24 · see citing works
Kaiser, M. I., & Trappes, R. (2021) · Biology & Philosophy · doi:10.1007/s10539-021-09791-5 · Cited by 28
“There is also evidence that differences arise amongst genetically identical individuals raised in the same environment (Vogt et al. 2008; Gärtner 2012; Freund et al. 2013; Vogt 2015; Bierbach et al. 2017).”
BackgroundHistone H4 acetylation regulates behavioral inter-individual variability in zebrafish
Román, A.-C., Vicente-Page, J., Pérez-Escudero, A., Carvajal-González, J. M., Fernández-Salguero, P., & de Polavieja, G. D. (2017) · Genome Biology · doi:10.1186/s13059-018-1428-y · Cited by 27 · see citing works
“Nevertheless, a pioneering study showed that there was variability independent of genetic differences in some morphological traits in mice raised in identical environments (Gärtner, 1990).”
BackgroundEmbryonic geometry underlies phenotypic variation in decanalized conditions
Huang, A.-Q., Rupprecht, J.-F., & Saunders, T. (2020) · eLife · doi:10.7554/elife.47380 · Cited by 26
- Authors
- Gärtner, K.
- Affiliations
- Medizinische Hochschule Hannover (DE)
- Corresponding author
- Gärtner, Klaus
- ORCID
- Gärtner, Klaus
- Venue
- Laboratory Animals
- Publisher
- SAGE Publications
- Published
- 1990-01-01
- Volume
- 24
- Issue
- 1
- Pages
- 71-77
- ISSN
- 0023-6772 (ISSN-L)
- 1758-1117
- OpenAlex
- W2110941726
- Cited by
- 241
- References
- 0
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 10 · 2022: 10 · 2021: 7 · 2020: 4 · 2019: 10 · 2018: 12 · 2017: 8 · 2016: 6 · 2015: 9 · 2014: 6 · 2013: 8 · 2012: 19
- FWCI
- 1.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Laboratory Animals (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
- Life Sciences › Agricultural and Biological Sciences › Ecology, Evolution, Behavior and Systematics › Animal Behavior and Reproduction
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Evolution and Genetic Dynamics
- Keywords
- random variation, phenotypic variability, inbred strains, body weight, postnatal environment, twin studies, natural selection, quantitative traits, inbred rat strains, inbred mouse strains
- MeSH terms
- Animals, Animal Husbandry, Animals, Laboratory, Body Weight, Environment, Genotype, Research Design, Genetic Variation, Normal Distribution, Mice, Rats
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