Development of the Nude Rabbit Model.

Jun Song,Yui Koike,Cheng Deng,Jie Xu,Changzhi Zhao,Mark Hoenerhoff,Dongshan Yang,Ying Yang,Bo Yang,Tomonari Koike,Brooke Pallas,Patrick Lester,Linyuan Ma,Luan Wen,Jifeng Zhang,Y Eugene Chen

doi:10.1016/j.stemcr.2021.01.010

Abstract

SummaryLoss-of-function mutations in the forkhead box N1 (FOXN1) gene lead to nude severe combined immunodeficiency, a rare inherited syndrome characterized by athymia, severe T cell immunodeficiency, congenital alopecia, and nail dystrophy. We recently produced FOXN1 mutant nude rabbits (NuRabbits) by using CRISPR-Cas9. Here we report the establishment and maintenance of the NuRabbit colony. NuRabbits, like nude mice, are hairless, lack thymic development, and are immunodeficient. To demonstrate the functional applications of NuRabbits in biomedical research, we show that they can successfully serve as the recipient animals in xenotransplantation experiments using human induced pluripotent stem cells or tissue-engineered blood vessels. Our work presents the NuRabbit as a new member of the immunodeficient animal model family. The relatively large size and long lifespan of NuRabbits offer unique applications in regenerative medicine, cancer research, and the study of a variety of other human conditions, including immunodeficiency.

Highlights

The nude mouse (NuMouse) as an experimental animal model has been well established and applied in diverse biomedical research fields, including immunology, cancer research, stem cell therapy, and skin regeneration (Zhang et al, 2012)
The nude phenotype is caused by mutation of the forkhead box N1 (FOXN1) gene, which plays a pivotal role in the differentiation of thymic and skin epithelial cells (Brissette et al, 1996; Grabowska and Wilanowski, 2017; Lee et al, 1999; Meier et al, 1999; Nowell et al, 2011; Zuklys et al, 2016)
In a stem cell teratoma assay, human embryonic stem cells (ESCs) or induced pluripotent stem cells are often transplanted into NuMice, in order to evaluate the growth rate and germ-layer origins of the resulting teratoma. This method represents the current gold standard for the functional evaluation of ESCs and iPSCs, regarding their capacity to differentiate into a diverse array of tissue types (Brivanlou et al, 2003; Hentze et al, 2009)

Summary

Introduction

The nude mouse (NuMouse) as an experimental animal model has been well established and applied in diverse biomedical research fields, including immunology, cancer research, stem cell therapy, and skin regeneration (Zhang et al, 2012). In a stem cell teratoma assay, human embryonic stem cells (ESCs) or induced pluripotent stem cells (iPSCs) are often transplanted into NuMice, in order to evaluate the growth rate and germ-layer origins of the resulting teratoma. This method represents the current gold standard for the functional evaluation of ESCs and iPSCs, regarding their capacity to differentiate into a diverse array of tissue types (Brivanlou et al, 2003; Hentze et al, 2009)

Results

Discussion

Conclusion