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

Journal Article · Sun Sep 01 04:00:00 EDT 1991 · Proceedings of the National Academy of Sciences of the United States of America; (United States)

DOI:https://doi.org/10.1073/pnas.88.17.7640· OSTI ID:5823122

Vandenberg, P; Khillan, J S; Prockop, D J; Helminen, H; Kontusaari, S; Ala-Kokko, L ^[1]

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1. Thomas Jefferson Univ., Philadelphia, PA (United States)

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.

• OSTI ID: 5823122
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (United States), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (United States) Vol. 88:17; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550200* -- Biochemistry
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BODY
CARBON 14 COMPOUNDS
CARBON COMPOUNDS
CARTILAGE
COLLAGEN
CONNECTIVE TISSUE
CONNECTIVE TISSUE CELLS
ELECTRON MICROSCOPY
GENE REGULATION
LABELLED COMPOUNDS
MAMMALS
MAN
MICE
MICROSCOPY
MORPHOLOGICAL CHANGES
ORGANIC COMPOUNDS
PHENOTYPE
PRIMATES
PROTEINS
RODENTS
SCLEROPROTEINS
SOMATIC CELLS
TISSUES
TRANSMISSION ELECTRON MICROSCOPY
VERTEBRATES