Assembly of type IV collagen - Insights from alpha 3(IV) collagen-deficient mice

Type IV collagen includes six genetically distinct polypeptides named alpha 1(IV) through alpha 6(IV). These isoforms are speculated to organize thems elves into unique networks providing mammalian basement membranes specifici ty and inequality. Recent studies using bovine and human glomerular and tes tis basement membranes have shown that unique networks of collagen comprisi ng either alpha 1 and alpha 2 chains or alpha 3, alpha 4, and alpha 5 chain s can be identified. These studies have suggested that assembly of alpha 5 chain into type IV collagen network is dependent on alpha 3 expression wher e both chains are normally present in the tissue. In the present study, we show that in the lens and inner ear of normal mice, expression of alpha 1, alpha 2, alpha 3, alpha 4, and alpha 5 chains of type IV collagen can be de tected using alpha chain-specific antibodies. In the alpha 3(IV) collagen-d eficient mice, only the expression of alpha 1, alpha 2, and alpha 5 chains of type IV collagen was detectable. The non-collagenous 1 domain of alpha 5 chain was associated with alpha 1 in the non-collagenous 1 domain hexamer structure, suggesting that network incorporation of alpha 5 is possible in the absence of the alpha 3 chain in these tissues. The present study proves that expression of alpha 5 is not dependent on the expression of alpha 3 c hain in these tissues and that alpha 5 chain can assemble into basement mem branes in the absence of alpha 3 chain. These findings support the notion t hat type IV collagen assembly may be regulated by tissue-specific factors.