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Generation and Phenotyping of Progranulin-Deficient Mice

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Progranulin and Central Nervous System Disorders

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Abstract

Progranulin (PGRN) is a multifunctional growth factor involved in many physiological and pathological processes in the brain. PGRN is expressed in a wide variety of tissues and organs including neural tissues, reproductive organs, endocrine organs, and gastrointestinal tract. We have previously reported that PGRN is one of the major factors involved in masculinization of the brain of rodents during neonatal period. To further evaluate the masculinizing role of PGRN, we have generated a line of PGRN-deficient mice. Male PGRN-deficient mice showed decreased ejaculation incidence and increased anxiety, implying the disrupted masculinization of the brain. We secondly focused on the PGRN function in the hippocampus and the cerebellum as those are the regions with high expression of PGRN in the brain. In the PGRN-deficient mice, the facilitative effect of voluntary exercise on adult hippocampal neurogenesis was blunted while the suppressive effect of immune challenge was exacerbated. Furthermore, PGRN-deficient mice showed a higher density of Purkinje cell dendrites in the molecular layer of the cerebellum, which possibly leads to the motor dysfunction we detected in those mice. In conclusion, we have demonstrated that PGRN functions to develop and maintain the neuronal circuits not only in the neonatal but also in the manured brain.

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Authors and Affiliations

  1. Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

    Takashi Matsuwaki

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  1. Takashi Matsuwaki
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Correspondence to Takashi Matsuwaki .

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Editors and Affiliations

  1. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan

    Hideaki Hara

  2. Dementia Research Project, Department of Dementia and Higher Brain Function, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan

    Masato Hosokawa

  3. Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan

    Shinsuke Nakamura

  4. Department of Neurology, Gifu University Graduate School of Medicine, Gifu, Japan

    Takayoshi Shimohata

  5. Department of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan

    Masugi Nishihara

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Matsuwaki, T. (2019). Generation and Phenotyping of Progranulin-Deficient Mice. In: Hara, H., Hosokawa, M., Nakamura, S., Shimohata, T., Nishihara, M. (eds) Progranulin and Central Nervous System Disorders. Springer, Singapore. https://doi.org/10.1007/978-981-13-6186-9_9

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