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Malformation of the Posterior Cerebellar Vermis Is a Common Neuroanatomical Phenotype of Genetically Engineered Mice on the C57BL/6 Background

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Abstract

C57BL/6 mice exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the posterior vermis, indicative of neuronal migration defect during cerebellar development. Recognizing that many genetically engineered (GE) mouse lines are produced from C57BL/6 ES cells or backcrossed to this strain, we performed histological analyses and found that cerebellar heterotopia were a common feature present in the majority of GE lines on this background. Furthermore, we identify GE mouse lines that will be valuable in the study of cerebellar malformations including diverse driver, reporter, and optogenetic lines. Finally, we discuss the implications that these data have on the use of C57BL/6 mice and GE mice on this background in studies of cerebellar development or as models of disease.

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Funding

Supported in part by NIH grant R01-NS088667 (JHW); FS was supported in part by NIH training grant T32-NS007413.

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Authors and Affiliations

  1. Department of Biomedical Sciences, College of Osteopathic Medicine, New York Institute of Technology, Northern Boulevard, PO Box 8000, Old Westbury, NY, 11568-8000, USA

    Joshua A. Cuoco, Anthony W. Esposito, Shannon Moriarty, Ying Tang, Sonika Seth, Alyssa R. Toia, Elias B. Kampton, Yevgeniy Mayr, Mussarah Khan, Mohammad B. Khan, Olga V. Savinova & Raddy L. Ramos

  2. Department of Molecular, Cell and Developmental Biology, University of California Santa Cruz, Santa Cruz, CA, 95064, USA

    Brian R. Mullen & James B. Ackman

  3. Division of Neurology and Research Institute of Children’s Hospital of Philadelphia, Philadelphia, PA, 19104, USA

    Faez Siddiqi & John H. Wolfe

  4. Department of Pediatrics, Perelman School of Medicine and W.F. Goodman Center for Comparative Medical Genetics, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA, USA

    John H. Wolfe

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  1. Joshua A. Cuoco
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  2. Anthony W. Esposito
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Correspondence to Raddy L. Ramos.

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Cuoco, J.A., Esposito, A.W., Moriarty, S. et al. Malformation of the Posterior Cerebellar Vermis Is a Common Neuroanatomical Phenotype of Genetically Engineered Mice on the C57BL/6 Background. Cerebellum 17, 173–190 (2018). https://doi.org/10.1007/s12311-017-0892-3

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