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

Lois J. Arend, Ann M. Smart, Josie P. Briggs

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)2297-2305
Number of pages9
JournalJournal of the American Society of Nephrology
Volume11
Issue number12
StatePublished - 2000

ASJC Scopus subject areas

  • Nephrology

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