title: The globular domain of the proalpha 1(I) N-propeptide is not required for secretion, processing by procollagen N-proteinase, or fibrillogenesis of type I collagen in mice.
abstract: The globular domain in the NH(2)-terminal propeptide (N-propeptide) of the proalpha1(I) chain is largely encoded by exon 2 of the Col1a1 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 Col1a1 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.
authors.affiliation: Department of Biochemistry, the University of Washington, Seattle, Washington 98195, USA. bornsten@u.washington.edu
authors.forename: Paul
authors.initials: P
authors.lastname: Bornstein
authors.forename: Vanessa
authors.initials: V
authors.lastname: Walsh
authors.forename: Jennifer
authors.initials: J
authors.lastname: Tullis
authors.forename: Emily
authors.initials: E
authors.lastname: Stainbrook
authors.forename: John F
authors.initials: JF
authors.lastname: Bateman
authors.forename: Sheriar G
authors.initials: SG
authors.lastname: Hormuzdi
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015139:Blotting, Southern; D019556:COS Cells; D003094:Collagen / Q000378:metabolism; D024042:Collagen Type I / Q000737:chemistry*; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D000071837:Fibrillins; D005347:Fibroblasts / Q000378:metabolism; D005838:Genotype; D007438:Introns; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000737:chemistry*; D008957:Models, Genetic; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D011347:Procollagen / Q000737:chemistry*; D011348:Procollagen N-Endopeptidase / Q000737:chemistry*; D011498:Protein Precursors / Q000737:chemistry; D017434:Protein Structure, Tertiary; D012867:Skin / Q000473:pathology; D014945:Wound Healing
chemical_list: D024042:Collagen Type I; D000071837:Fibrillins; D008840:Microfilament Proteins; D010455:Peptides; D011347:Procollagen; D011498:Protein Precursors; D003094:Collagen; D011348:Procollagen N-Endopeptidase