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Title: Expression of a partially deleted gene of human type II procollagen (COL2A1) in transgenic mice produces a chondrodysplasia

A minigene version of the human gene for type II procollagen (COL2AI) 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:
; ; ; ; ;  [1]
  1. (Thomas Jefferson Univ., Philadelphia, PA (United States))
Publication Date:
OSTI Identifier:
5823122
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States); Journal Volume: 88:17
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; CARTILAGE; TRANSMISSION ELECTRON MICROSCOPY; COLLAGEN; GENE REGULATION; CARBON 14 COMPOUNDS; CONNECTIVE TISSUE CELLS; MAN; MICE; MORPHOLOGICAL CHANGES; PHENOTYPE; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; BODY; CARBON COMPOUNDS; CONNECTIVE TISSUE; ELECTRON MICROSCOPY; LABELLED COMPOUNDS; MAMMALS; MICROSCOPY; ORGANIC COMPOUNDS; PRIMATES; PROTEINS; RODENTS; SCLEROPROTEINS; SOMATIC CELLS; TISSUES; VERTEBRATES 550200* -- Biochemistry