Mouse β₆ integrin sequence, pattern of expression, and role in kidney development

Integrins mediate cell-cell and cell-extracellular matrix interactions and play key roles in development. β₆ integrin expression has been demonstrated in human fetal kidney at a higher level than in the adult, making β₆ integrin a marker of interest for the study of development of the nephron. The aims of this study were to determine the cDNA sequence for the mouse β₆ integrin and to characterize β₆ integrin expression in the developing mouse kidney. Two embryonic mouse kidney cDNA libraries were screened, and the coding region was sequenced. The mouse β₆ nucleotide coding region sequence shows 82% nucleotide identity to the human sequence. The putative amino acid sequence has 89.5% identity to human β₆ integrin and contains many conserved domains. By reverse transcription-PCR, β₆ integrin mRNA expression is very low at 11 d of gestation in the mouse, increases dramatically by E14 and E17 (20-fold, normalized for increases in β actin), and plateaus by 2 wk of age. β₆ integrin expression is induced 15- to 20-fold after 5 d in metanephric explant culture. Reverse transcription-PCR of adult rat microdissected nephron segments demonstrates β₆ integrin mRNA expression in proximal tubule, cortical thick ascending limb, distal nephron segments (inner and outer medullary collecting ducts), and macula densa-containing segments. Lectin-peroxidase and in situ colocalization studies demonstrated expression of β₆ integrin mRNA in developing proximal tubules and thick ascending limb. Culture of mouse metanephric kidneys with antisense oligonucleotides to β₆ integrin resulted in inhibition of ureteric bud branching and complete lack of mesenchyme condensation. These studies demonstrate a high homology between the human and mouse β₆ integrin sequence, a different pattern of expression in the developing mouse kidney compared with the primate kidney, and abnormal metanephric development in culture in the absence of β₆ integrin. These findings suggest an important role for β₆ integrin in normal development of the mouse kidney.