title: Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia.
abstract: A minigene version of the human gene for type II procollagen (COL2A1) was prepared that lacked a large central region containing 12 of the 52 exons and therefore 291 of the 1523 codons of the gene. The construct was modeled after sporadic in-frame deletions of collagen genes that cause synthesis of shortened pro alpha chains that associate with normal pro alpha chains and thereby cause degradation of the shortened and normal pro alpha chains through a process called procollagen suicide. The gene construct was used to prepare five lines of transgenic mice expressing the minigene. A large proportion of the mice expressing the minigene developed a phenotype of a chondrodysplasia with dwarfism, short and thick limbs, a short snout, a cranial bulge, a cleft palate, and delayed mineralization of bone. A number of mice died shortly after birth. Microscopic examination of cartilage revealed decreased density and organization of collagen fibrils. In cultured chondrocytes from the transgenic mice, the minigene was expressed as shortened pro alpha 1(II) chains that were disulfide-linked to normal mouse pro alpha 1(II) chains. Therefore, the phenotype is probably explained by depletion of the endogenous mouse type II procollagen through the phenomenon of procollagen suicide.
authors.affiliation: Department of Biochemistry and Molecular Biology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
authors.forename: P
authors.initials: P
authors.lastname: Vandenberg
authors.forename: J S
authors.initials: JS
authors.lastname: Khillan
authors.forename: D J
authors.initials: DJ
authors.lastname: Prockop
authors.forename: H
authors.initials: H
authors.lastname: Helminen
authors.forename: S
authors.initials: S
authors.lastname: Kontusaari
authors.forename: L
authors.initials: L
authors.lastname: Ala-Kokko
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002113:Calcification, Physiologic; D002356:Cartilage / Q000473:pathology; D002806:Chondrodysplasia Punctata / Q000235:genetics* / Q000473:pathology; D002872:Chromosome Deletion; D003062:Codon / Q000235:genetics; D005091:Exons; D005796:Genes; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D010641:Phenotype; D011347:Procollagen / Q000235:genetics*; D015183:Restriction Mapping
chemical_list: D003062:Codon; D011347:Procollagen