Work

The loss of keratin 77 in murine skin is functionally compensated by keratin 1

Year: 2024

Type: article

Abstract: Keratins, the intermediate filament-forming proteins of the epithelial cells, are mainly expressed in keratinocytes, preserving the structural integrity and cohesion of the epidermis. There are multiple inherited skin conditions arising from mutations in the encoding genes of specific keratins, highlighting their significance in skin health. Furthermore, the aberrant expression of keratins is evidenced in certain skin diseases, such as psoriasis, atopic dermatitis, and skin cancer. Keratin 77 (KRT77) is a type II keratin with demonstrated expression in human and mouse sweat glands' ducts. Using the CRISPR/Cas9 technique, we generated a Krt77 -deficient ( Krt77 -KO) mouse line to reveal its obscure function in skin biology and homeostasis. KRT77 loss did not result in any fetal lethality or detrimental impact on the development of the skin and its appendages. However, we identified a substantially increased expression of KRT1 in the skin of the Krt77 -KO mouse line in comparison with control littermates at both mRNA and protein levels using RT-qPCR and western blot analyses, respectively. Based on these findings, we concluded that the absence of KRT77 in the murine skin leads to upregulation of KRT1, an alternative epidermal type II keratin within the same subfamily as KRT77, which rescues the lack of KRT77. • Krt77 is expressed in several tissues as skin, brain, buccal mucosa, and stomach. • Generation of a novel ubiquitous knockout mouse line for KRT77. • Loss of KRT77 did not affect mouse development, fertility, or skin homeostasis. • KRT77 knockout mice show increased expression of Krt1 , Krt10 , and Krt9 in the skin. • A deletion of KRT77 is counterbalanced by KRT1.

Source: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research

DOI: 10.1016/j.bbamcr.2024.119881