Altered gene expression in slc4a11−/− mouse cornea highlights SLC4A11 roles

• Published in: Scientific reports Vol. 11; no. 1; p. 20885
• Main Authors: Alvarez, Bernardo V., Piché, Marilyse, Aizouki, Carolin, Rahman, Fariha, Derry, Jonathan M. J., Brunette, Isabelle, Casey, Joseph R.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 22-10-2021; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/337; 631/443; 631/45; 631/80; 692/4017; Adhesion; Ammonia; Animals; Anion Transport Proteins - genetics; Cell adhesion; Cell adhesion & migration; Cell Adhesion - genetics; Cell fate; Cell Membrane - genetics; Cornea; Cornea - physiology; Corneal dystrophy; Cytoskeleton; Dystrophy; Endothelial cells; Endothelial Cells - physiology; Endothelium, Corneal - physiology; Energy metabolism; Epithelial Cells - physiology; Extracellular matrix; Extracellular Matrix - genetics; Gene expression; Gene Expression - genetics; Gene Expression Regulation - genetics; Genomes; Homeostasis; Humanities and Social Sciences; Ion Transport - genetics; Male; Metabolism; Mice; multidisciplinary; Mutation - genetics; Polymerase chain reaction; Protein transport; Reverse transcription; Science; Science (multidisciplinary); Symporters - genetics; Urea; Water transport
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-021-98921-w

SLC4A11 is a H
+
/NH
3
/water transport protein, of corneal endothelial cells. SLC4A11 mutations cause congenital hereditary endothelial dystrophy and some cases of Fuchs endothelial corneal dystrophy. To probe SLC4A11’s roles, we compared gene expression in RNA from corneas of 17-week-old
slc4a11
−/−
(n = 3) and
slc4a11
+
/
+
mice (n = 3) and subjected to RNA sequencing. mRNA levels for a subset of genes were also assessed by quantitative real-time reverse transcription PCR (qRT RT-PCR). Cornea expressed 13,173 genes, which were rank-ordered for their abundance. In
slc4a11
−/−
corneas, 100 genes had significantly altered expression. Abundant
slc14a1
expression, encoding the urea transporter UT-A, suggests a significant role in the cornea. The set of genes with altered expression was subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses, revealing that alterations clustered into extracellular region, cytoskeleton, cell adhesion and plasma membrane functions. Gene expression changes further clustered into classes (with decreasing numbers of genes): cell fate and development, extracellular matrix and cell adhesion, cytoskeleton, ion homeostasis and energy metabolism. Together these gene changes confirm earlier suggestions of a role of SLC4A11 in ion homeostasis, energy metabolism, cell adhesion, and reveal an unrecognized SLC4A11 role in cytoskeletal organization.