The globular domain of the proα1(I) N-propeptide is not required for secretion, processing by procollagen N-proteinase, or fibrillogenesis of type I collagen in mice

Paul Bornstein, Vanessa Walsh, Jennifer Tullis, Emily Stainbrook, John F. Bateman, Sheriar G. Hormuzdi

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)

    Abstract

    The globular domain in the NH-terminal propeptide (N-propeptide) of the proa1(I) chain is largely encoded by exon 2 of the Colla1 gene and has been implicated in a number of processes that are involved in the biogenesis, maturation, and function of type I collagen. These include intracellular chain association, transcellular transport and secretion, proteolytic processing of the precursor, feedback regulation of synthesis, and control of fibrillogenesis. However, none of these proposed functions has been firmly established. To evaluate the function of this procollagen domain we have used a targeted mutagenesis approach to generate mice that lack exon 2 in the Colla1 gene. Mouse lines were established on both a mixed 129 OlaHsd/Sv and C57BL/6 background and a pure 129 OlaHsd/Sv background. Adult mice on the mixed background are normal in appearance and are fertile. To the extent that they have been studied, procollagen synthesis, secretion, and proteolytic processing are normal in these mice, and collagen fibrillogenesis is only slightly altered. However, breeding of heterozygous mutant mice on the 129 background generated homozygous mutants at only 64% of the expected frequency. These findings suggest that although the N-propeptide is not essential for collagen biogenesis in mice it may play some essential role during embryonic development.

    Original languageEnglish
    Pages (from-to)2605-2613
    Number of pages9
    JournalJournal of Biological Chemistry
    Volume277
    Issue number4
    DOIs
    Publication statusPublished - 25 Jan 2002

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