Mouse beta(6) integrin sequence, pattern of expression, and role in kidneydevelopment

Integrins mediate cell-cell and cell-extracellular matrix interactions and play key roles in development. beta (6) integrin expression has been demons trated in human fetal kidney at a higher level than in the adult, making be ta (6) integrin a marker of interest for the study of development of the ne phron. The aims of this study were to determine the cDNA sequence for the m ouse beta (6) integrin and to characterize beta (6) integrin expression in the developing mouse kidney. Two embryonic mouse kidney cDNA libraries were screened, and the coding region was sequenced. The mouse beta (6) nucleoti de coding region sequence shows 82% nucleotide identity to the human sequen ce. The putative amino acid sequence has 89.5% identity to human beta (6) i ntegrin and contains many conserved domains. By reverse transcription-PCR, beta (6) integrin mRNA expression is very low at 11 d of gestation in the m ouse, increases dramatically by E14 and E17 (20-fold, normalized for increa ses in beta actin), and plateaus by 2 wk of age. beta (6) integrin expressi on is induced 15- to 20-fold after 5 d in metanephric explant culture. Reve rse transcription-PCR of adult rat microdissected nephron segments demonstr ates beta (6) integrin mRNA expression in proximal tubule, cortical thick a scending limb, distal nephron segments (inner and outer medullary collectin g ducts), and macula densa-containing segments. Lectin-peroxidase and in si tu colocalization studies demonstrated expression of beta (6) integrin mRNA in developing proximal tubules and thick ascending limb. Culture of mouse metanephric kidneys with antisense oligonucleotides to beta (6) integrin re sulted in inhibition of ureteric bud branching and complete lack of mesench yme condensation. These studies demonstrate a high homology between the hum an and mouse beta (6) integrin sequence, a different pattern of expression in the developing mouse kidney compared with the primate kidney, and abnorm al metanephric development in culture in the absence of beta (6) integrin. These findings suggest an important role for beta (6) integrin in normal de velopment of the mouse kidney.