Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis

Hung Chih Chen, Yu Feng Chin, David J. Lundy, Chung Tiang Liang, Ya Hui Chi, Paolin Kuo, Patrick C.H. Hsieh

Research output: Contribution to journalArticle

Abstract

Duchenne muscular dystrophy (DMD) is an X-linked genetic disorder resulting from mutations in the dystrophin gene. The mdx/utrn -/- mouse, lacking in both dystrophin and its autosomal homologue utrophin, is commonly used to model the clinical symptoms of DMD. Interestingly, these mice are infertile but the mechanisms underlying this phenomenon remain unclear. Using dystrophin deficient mdx mouse and utrophin haplodeficient mdx/utrn +/- mouse models, we demonstrate the contribution of Dp427 (full-length dystrophin) and utrophin to testis and epididymis development, as well as spermatogenesis. We show that Dp427 deficiency disturbed the balance between proliferation and apoptosis of germ cells during spermatogenesis, which was further disrupted with utrophin haplodeficiency, deciphering a compensatory role of utrophin for dystrophin in the male reproductive system. In the spermatozoa, we have found a compensatory response of utrophin to dystrophin deficiency - namely the upregulation and relocation of utrophin to the flagellar midpiece. This study demonstrates the contribution of Dp427 and utrophin in male fertility, suggesting a potential pathology in DMD patients.

Original languageEnglish
Article number7372
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - Dec 1 2017
Externally publishedYes

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Utrophin
Dystrophin
Spermatogenesis
Inbred mdx Mouse
Duchenne Muscular Dystrophy
Inborn Genetic Diseases
Epididymis
Germ Cells
Fertility
Spermatozoa
Testis
Up-Regulation
Apoptosis
Pathology
Mutation

ASJC Scopus subject areas

  • General

Cite this

Chen, H. C., Chin, Y. F., Lundy, D. J., Liang, C. T., Chi, Y. H., Kuo, P., & Hsieh, P. C. H. (2017). Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis. Scientific Reports, 7(1), [7372]. https://doi.org/10.1038/s41598-017-05993-8

Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis. / Chen, Hung Chih; Chin, Yu Feng; Lundy, David J.; Liang, Chung Tiang; Chi, Ya Hui; Kuo, Paolin; Hsieh, Patrick C.H.

In: Scientific Reports, Vol. 7, No. 1, 7372, 01.12.2017.

Research output: Contribution to journalArticle

Chen, HC, Chin, YF, Lundy, DJ, Liang, CT, Chi, YH, Kuo, P & Hsieh, PCH 2017, 'Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis', Scientific Reports, vol. 7, no. 1, 7372. https://doi.org/10.1038/s41598-017-05993-8
Chen, Hung Chih ; Chin, Yu Feng ; Lundy, David J. ; Liang, Chung Tiang ; Chi, Ya Hui ; Kuo, Paolin ; Hsieh, Patrick C.H. / Utrophin Compensates dystrophin Loss during Mouse Spermatogenesis. In: Scientific Reports. 2017 ; Vol. 7, No. 1.
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