Alopecia in Harlequin mutant mice is associated with reduced AIF protein levels and expression of retroviral elements

Maik Hintze,Marion Michels,Daniele Bano,Birgit Blanck,Thomas Franz,Dieter Hartmann,Sebastian Griesing,Lena Wischhof

doi:10.1007/s00335-020-09854-0

Abstract

We investigated the contribution of apoptosis-inducing factor (AIF), a key regulator of mitochondrial biogenesis, in supporting hair growth. We report that pelage abnormalities developed during hair follicle (HF) morphogenesis in Harlequin (Hq) mutant mice. Fragility of the hair cortex was associated with decreased expression of genes encoding structural hair proteins, though key transcriptional regulators of HF development were expressed at normal levels. Notably, Aifm1 (R200 del) knockin males and Aifm1(R200 del)/Hq females showed minor hair defects, despite substantially reduced AIF levels. Furthermore, we cloned the integrated ecotropic provirus of the Aifm1Hq allele. We found that its overexpression in wild-type keratinocyte cell lines led to down-regulation of HF-specific Krt84 and Krtap3-3 genes without altering Aifm1 or epidermal Krt5 expression. Together, our findings imply that pelage paucity in Hq mutant mice is mechanistically linked to severe AIF deficiency and is associated with the expression of retroviral elements that might potentially influence the transcriptional regulation of structural hair proteins.

Highlights

As an appendage of the skin, hair follicles (HF) represent a complex miniorgan that consists of several concentric layers of epithelial cells forming the outer root sheath (ORS) in continuity with the epidermis, the inner root sheath (IRS), and the hair shaft
Reduced apoptosis-inducing factor (AIF) expression is linked to hair loss in Harlequin mutant mice The pelage defect of hemizygous Aifm1Hq/Y mice is apparent as early as postnatal day 9 (P9), when the tips of the hair shafts became visible on the skin surface, but did not elongate further in contrast to wild-type littermates (Fig. 1A.a)
This study shows that the pelage defect of the “Harlequin” (Hq) mutant is caused by the fragility of subapical parts of the hair shafts

Summary

Introduction

As an appendage of the skin, hair follicles (HF) represent a complex miniorgan that consists of several concentric layers of epithelial cells forming the outer root sheath (ORS) in continuity with the epidermis, the inner root sheath (IRS), and the hair shaft. The latter comprises the cuticle surrounding the cortex and a central medulla. Throughout the life of an organism, HFs constantly undergo phases of growth (anagen), regression (catagen), and rest (telogen)

Present Address

Results

Discussion

Ethics statement

Compliance with ethical standards