High incidence of sebaceous gland inflammation in aldose reductase-deficient mice

• Published in: Chemico-biological interactions 2024-04, Vol.392, p.110905-110905, Article 110905
• Main Authors: Mandava, Anjali, Pham, Binhan, Pedler, Michelle, Shieh, Biehuoy, Gopalakrishnan, Hari, Petrash, J. Mark
• Format: Article
• Language: English
• Subjects: Aldehyde Reductase - genetics; Aldose reductase; Animals; Capsule Opacification - pathology; Cataract - genetics; Cataract - pathology; CRISPR-Cas9; Epithelial-to-mesenchymal transition; Incidence; Inflammation - pathology; Lens, Crystalline - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Polyol pathway; Sebaceous gland; Sebaceous Glands
• ISSN: 0009-2797; 1872-7786
• DOI: 10.1016/j.cbi.2024.110905

Aldose reductase is a member of the 1B1 subfamily of aldo-keto reductase gene superfamily. The action of aldose reductase (AR) has been implicated in the pathogenesis of a variety of disease states, most notably complications of diabetes mellitus including neuropathy, retinopathy, nephropathy, and cataracts. To explore for mechanistic roles for AR in disease pathogenesis, we established mutant strains produced using Crispr-Cas9 to inactivate the AKR1B3 gene in C57BL6 mice. Phenotyping AR-knock out (ARKO) strains confirmed previous reports of reduced accumulation of tissue sorbitol levels. Lens epithelial cells in ARKO mice showed markedly reduced epithelial-to-mesenchymal transition following lens extraction in a surgical model of cataract and posterior capsule opacification. A previously unreported phenotype of preputial sebaceous gland swelling was observed frequently in male ARKO mice homozygous for the mutant AKR1B3 allele. This condition, which was shown to be accompanied by infiltration of proinflammatory CD3+ lymphocytes, was not observed in WT mice or mice heterozygous for the mutant allele. Despite this condition, reproductive fitness of the ARKO strain was indistinguishable from WT mice housed under identical conditions. These studies establish the utility of a new strain of AKR1B3-null mice created to support mechanistic studies of cataract and diabetic eye disease. •AKR1B3-null mice (ARKO) were produced by Crispr-Cas9-mediated gene disruption.•ARKO mice demonstrate reduced EMT response following lens extraction.•ARKO mice are at increased risk for development of preputial gland inflammation.