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Efficient quantitative morphological phenotyping of genetically altered organisms using stereology

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Abstract

Genetically modified organisms present the challenge of quantifying structures and functions in organs, tissues and cells. Morphological investigation is greatly facilitated by taking sections in MRI, CAT scanning, histological preparations or EM, and powerful unbiased quantitative tools called stereology can use these sections in a sampling based approach to measure volume, number surface and length. Stereological tools have become methods of choice in the fields of neurobiology, nephrology and cell biology and allow accurate unbiased description of intact organs, tissues, cells and organelles. Stereology has yet to be applied widely in the field of transgenics. Here I provide an overview of stereological methods and explain how they represent a powerful addition to the transgenic biologists armoury of techniques.

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Notes

  1. Stereology can also be used to quantify the spatial distribution of biological quantities—using so called second-order stereology. This is outside the scope of this article but the reader is referred to sample papers that deal with this subject (Diggle 1983; Krasnoperov and Stoyan 2004; Mattfeldt 2005; Mattfeldt et al. 2006; Mayhew 1999; Nyengaard and Gundersen 2006; Prior et al. 2003; Reed and Howard 1999; Ripley 1981).

  2. It is important to note here that over the past 20 years there has been a move away from techniques that quantify on the basis of model assumptions about the size, shape or number of structures e.g. that a nucleus is spherical or a tubule is a cylinder. Modern stereology is designed a priori to remove restrictions of these assumptions and to provide unbiased estimates no matter what biological object is examined. These methods are therefore designated design-based estimators. They can be used to measure the aggregate volume, surface and length of a biological object of interest as well as the volume, surface, length and number of its individual components.

  3. In general SR sampling is more efficient on the inhomogeneous samples that abound in biology. However, when a periodic structure is in register with the array of the systematic sample then estimates can be more variable (less precise) than those obtained with random sampling. Simple random sampling is then the method of choice.

  4. With a growing number of experts in the field there are increasing opportunities to gain invaluable assistance in the initial phases of a project (see the International Society of Stereology website at http://www.stereologysociety.org/).

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Acknowledgements

The author is grateful to the College of Life Sciences and the University of Dundee for continuing support of quantitative morphological approaches.

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  1. Division of Cell Biology and Immunology, Wellcome Trust Biocentre, College of Life Sciences, University of Dundee, DD1 5EH, Scotland, UK

    John Milton Lucocq

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Lucocq, J.M. Efficient quantitative morphological phenotyping of genetically altered organisms using stereology. Transgenic Res 16, 133–145 (2007). https://doi.org/10.1007/s11248-006-9048-9

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