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Principal Component and Cluster Analysis of Morphological Variables Reveals Multiple Discrete Sub-phenotypes in Weaver Mouse Mutants

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Abstract

The present study evaluates the usefulness of the principal component analysis-based cluster analysis in the categorization of several sub-phenotypes in the weaver mutant by using several morphological parameters from the cerebellar cortex of control, heterozygous (+/wv) and homozygous (wv/wv) weaver mice. The quantified parameters were length of the cerebellar cortex, area of the external granular layer, area of the molecular layer, number of the external granular layer cells (EGL), and number of Purkinje cells (PCs). The analysis indicated that at postnatal day 8, the genotype +/wv presented three sub-phenotypes tagged as +/wv 0, +/wv 1 and +/wv 2, whereas two sub-phenotypes designated as wv 0/wv 1 and wv 0/wv 2 were identified in the genotype wv/wv. The number of PCs for the genotype +/wv and the number of EGL cells for the genotype wv/wv were the variables that discriminated the best among sub-phenotypes. Each one of the sub-phenotypes showed specific abnormalities in the cytoarchitecture of the cerebellar cortex as well as in the foliar pattern. In particular, the wv 0/wv 1 and wv 0/wv 2 sub-phenotypes had the most altered cytoarchitectonics, followed by the +/wv 2 sub-phenotype and then by the +/wv 1 one. The sub-phenotype +/wv 0 was the less affected one. Apart from reporting for the first time the coexistence of several sub-phenotypes in the weaver mutant, our approach provides a new statistical tool that can be used to assess cerebellar morphology.

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Acknowledgments

The authors are very grateful to Dr. Shirley A. Bayer for providing weaver mice. This research was supported by grants, FIS10-00975, FMM-08, SGR2009-00761.

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Authors and Affiliations

  1. Departament de Biologia Cel.lular, de Fisiologia i d’Immunologia. Unidad de Citologia i d’Histologia. Facultat de Biociències, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain

    Joaquín Martí, María C. Santa-Cruz, Roger Serra, Vanessa Molina & José P. Hervás

  2. Servei d’Estadística Aplicada, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain

    Oliver Valero

  3. Departament de Bioquímica i Biologia Molecular. Facultat de Biociències, Universitat Autònoma de Barcelona, 08193, Bellaterra, Barcelona, Spain

    Sandra Villegas

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  1. Joaquín Martí
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  2. María C. Santa-Cruz
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  3. Roger Serra
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  4. Oliver Valero
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  5. Vanessa Molina
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Correspondence to Joaquín Martí or Sandra Villegas.

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Martí, J., Santa-Cruz, M.C., Serra, R. et al. Principal Component and Cluster Analysis of Morphological Variables Reveals Multiple Discrete Sub-phenotypes in Weaver Mouse Mutants. Cerebellum 12, 406–417 (2013). https://doi.org/10.1007/s12311-012-0429-8

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  • DOI: https://doi.org/10.1007/s12311-012-0429-8

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