Kindlin-1 mutant zebrafish as an in vivo model system to study adhesion mechanisms in the epidermis.

[kindler syndrome]

From a forward genetic screen for epidermal defects in zebrafish , we identified a loss -of-function mutation in Kindlin-1 , an essential regulator of integrin function . The mutation generates a premature stop codon , deleting the integrin-binding site . The mutant zebrafish develops cell-matrix and cell-cell adhesion defects in the basal epidermis leading to progressive fin rupturing , and was therefore designated rupturing-of-fins (rof ). Similar defects were observed in the epidermis of Kindler syndrome patients , carrying a loss -of-function mutation in kindlin-1 . Mutational analysis and rescue experiments in zebrafish revealed that residues K 610 , W 612 , and I 647 in the F 3 domain are essential for Kindlin-1 function in vivo , and that Kindlin-2 can functionally compensate for the loss of Kindlin-1 . The fin phenotype of rof /kindlin-1 mutants resembles that of badfin mutants , carrying a mutation in integrin Î±3 . We show here that this mutation impairs the biosynthesis of integrin Î±3 Î² 1 and causes cell-matrix and cell-cell defects in vivo . Whereas both Integrin-linked kinase (Ilk ) and Kindlin-1 cooperate with Integrin Î±3 Î² 1 to resist trauma-induced epidermal defects , Kindlin-1 and Ilk , surprisingly , do not act synergistically but in parallel . Thus , the rof /kindlin-1 mutant zebrafish provides a unique model system to study epidermal adhesion mechanisms in vivo .

Diseases
Validation

Diseases presenting "deleting the integrin-binding site" symptom

kindler syndrome

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