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

Journal Article · Sun Sep 01 00:00:00 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), Vol. 88:17; ISSN 0027-8424
• Country of Publication: United States
• Language: English

Related Subjects

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