Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations

Takahashi, Ryo; Takahashi, Gou; Kameyama, Yuichi; Sato, Masahiro; Ohtsuka, Masato; Wada, Kenta

doi:10.3390/ijms231911855

Open AccessArticle

Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations

by

Ryo Takahashi

¹,

Gou Takahashi

²

,

Yuichi Kameyama

¹,

Masahiro Sato

³

,

Masato Ohtsuka

^4,5,6

and

Kenta Wada

^1,*

¹

Graduate School of Bioindustry, Tokyo University of Agriculture, Abashiri 099-2493, Japan

²

Regenerative Medicine Project, Tokyo Metropolitan Institute of Medical Science, Tokyo 156-8506, Japan

³

Department of Genome Medicine, National Center for Child Health and Development, Tokyo 157-8535, Japan

⁴

Department of Molecular Life Science, Division of Basic Medical Science and Molecular Medicine, Tokai University School of Medicine, Isehara 259-1193, Japan

⁵

Center for Matrix Biology and Medicine, Graduate School of Medicine, Tokai University, Isehara 259-1193, Japan

⁶

The Institute of Medical Sciences, Tokai University, Isehara 259-1193, Japan

^*

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2022, 23(19), 11855; https://doi.org/10.3390/ijms231911855

Submission received: 24 August 2022 / Revised: 27 September 2022 / Accepted: 3 October 2022 / Published: 6 October 2022

(This article belongs to the Special Issue Gene Editing and Delivery in Animal Genetic Engineering)

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Abstract

Fibroblast growth factor 5 (FGF5) is an important molecule required for the transition from anagen to catagen phase of the mammalian hair cycle. We previously reported that Syrian hamsters harboring a 1-bp deletion in the Fgf5 gene exhibit excessive hair growth in males. Herein, we generated Fgf5 mutant mice using genome editing via oviductal nucleic acid delivery (GONAD)/improved GONAD (i-GONAD), an in vivo genome editing system used to target early embryos present in the oviductal lumen, to study gender differences in hair length in mutant mice. The two lines (Fgf5^go-malc), one with a 2-bp deletion (c.552_553del) and the other with a 1-bp insertion (c.552_553insA) in exon 3 of Fgf5, were successfully established. Each mutation was predicted to disrupt a part of the FGF domain through frameshift mutation (p.Glu184ValfsX128 or p.Glu184ArgfsX128). Fgf5^go-malc1 mice had heterogeneously distributed longer hairs than wild-type mice (C57BL/6J). Notably, this change was more evident in males than in females (p < 0.0001). Immunohistochemical analysis revealed the presence of FGF5 protein in the dermal papilla and outer root sheath of the hair follicles from C57BL/6J and Fgf5^go-malc1 mice. Histological analysis revealed that the prolonged anagen phase might be the cause of accelerated hair growth in Fgf5^go-malc1 mice.

Keywords: fibroblast growth factor 5; long-haired mice; gender difference; genome editing; hair follicle cycle; GONAD; indels; CRISPR/Cas9

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MDPI and ACS Style

Takahashi, R.; Takahashi, G.; Kameyama, Y.; Sato, M.; Ohtsuka, M.; Wada, K. Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations. Int. J. Mol. Sci. 2022, 23, 11855. https://doi.org/10.3390/ijms231911855

AMA Style

Takahashi R, Takahashi G, Kameyama Y, Sato M, Ohtsuka M, Wada K. Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations. International Journal of Molecular Sciences. 2022; 23(19):11855. https://doi.org/10.3390/ijms231911855

Chicago/Turabian Style

Takahashi, Ryo, Gou Takahashi, Yuichi Kameyama, Masahiro Sato, Masato Ohtsuka, and Kenta Wada. 2022. "Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations" International Journal of Molecular Sciences 23, no. 19: 11855. https://doi.org/10.3390/ijms231911855

APA Style

Takahashi, R., Takahashi, G., Kameyama, Y., Sato, M., Ohtsuka, M., & Wada, K. (2022). Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations. International Journal of Molecular Sciences, 23(19), 11855. https://doi.org/10.3390/ijms231911855

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Gender-Difference in Hair Length as Revealed by Crispr-Based Production of Long-Haired Mice with Dysfunctional FGF5 Mutations

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