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Developmental regulation for collagen II gene expression in transgenic mice
L A Bruggeman1, H X Xie, K S Brown
1Laboratory of Developmental Biology, National Institute of Dental Research, Bethesda, Maryland 20892.
Teratology
|August 1, 1991
Summary
Type II collagen regulatory sequences are crucial for development. Disrupting their expression using a diphtheria toxin gene construct led to severe developmental abnormalities and fetal death in transgenic mice.
Area of Science:
- Developmental Biology
- Genetics
- Molecular Biology
Background:
- Type II collagen is essential for cartilage formation and skeletal development.
- Understanding the regulatory sequences of type II collagen is key to studying chondrogenesis and related disorders.
Purpose of the Study:
- To investigate the role of type II collagen regulatory sequences in embryonic development.
- To assess the impact of targeted gene disruption in chondrocytes during development.
Main Methods:
- Construction and injection of a pDAS10-DTA plasmid containing the diphtheria toxin A chain gene under the control of rat type II collagen promoter and enhancer sequences.
- Gestation monitoring and examination of developing fetuses at various stages.
- Histological analysis of normal and abnormal fetal tissues.
Main Results:
- Injection of the construct resulted in a high incidence of aborted implants and severely malformed fetuses.
- Abnormal fetuses exhibited characteristics of chondrodysplasia, including small size, limb defects, and cleft palates.
- Histological examination revealed reduced extracellular matrix and disorganized chondrocyte tissue in affected fetuses, indicating successful toxin expression in chondrocytes.
Conclusions:
- Type II collagen promoter and enhancer sequences direct developmental expression, crucial for chondrocyte survival and proper skeletal formation.
- Disruption of type II collagen gene expression during development leads to severe chondrodystrophic phenotypes.
- These findings highlight the critical role of type II collagen regulation in skeletal morphogenesis.