Abnormal craniofacial development and expression patterns of extracellular matrix components in transgenic Del1 mice harboring a deletion mutation in the type II collagen gene.
OBJECTIVE
To analyze the effect of a type II collagen mutation on craniofacial development in transgenic Del1 mice.


METHODS
Samples from homozygous (+/+) and heterozygous (+/-) transgenic Del1 mice harboring mutations in the type II collagen gene as well as non-transgenic (-/-) littermates were collected at days 12.5, 14.5, 16.5 and 18.5 of gestation. The cartilaginous and bony elements of the craniofacial skeleton were analyzed after staining with alcian blue, alizarin red S and von Kossa. The expression patterns of type II, IX and X collagens and aggrecan were analyzed by immunohistochemistry and in situ hybridization.


RESULTS
Several abnormalities were observed in the craniofacial skeleton of transgenic Del1 mice. These include an overall retardation of chondrogenesis and osteogenesis in Del1 +/+ mice, and to a lesser extent also in Del1+/- mice. Characteristic findings in Del1 +/+ mice included a reduced anterioposterior length, a smaller size of the mandible, a palatal cleft and a downward bending snout. We also detected retarded ossification of calvarial bones in Del1 +/+ and +/- mice when compared with Del1 -/- mice. A surprising finding was the presence of both type II and X collagens and their mRNAs in the periosteum of the cranial base.


CONCLUSIONS
The present study confirms the important role of type II collagen mutation in craniofacial development and growth. In addition to affecting endochondral ossification, the type II collagen mutation also disturbs intramembranous ossification in the developing craniofacial skeleton.
Savontaus
M
M
Department of Medical Biochemistry and Molecular Biology, University of Turku, Turku, Finland.
Rintala-Jämsä
M
M
Morko
J
J
Rönning
O
O
Metsäranta
M
M
Vuorio
E
E
D000818:Animals; D020219:Chondrogenesis / Q000235:genetics; D002972:Cleft Palate / Q000235:genetics; D024043:Collagen Type II / Q000235:genetics*; D024081:Collagen Type IX / Q000235:genetics; D024121:Collagen Type X / Q000235:genetics; D019465:Craniofacial Abnormalities / Q000235:genetics*; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D017353:Gene Deletion; D005865:Gestational Age; D006579:Heterozygote; D006720:Homozygote; D008334:Mandible / Q000002:abnormalities; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation / Q000235:genetics*; D009295:Nasal Bone / Q000002:abnormalities; D010012:Osteogenesis / Q000235:genetics; D019291:Skull Base / Q000002:abnormalities; D013997:Time Factors
D024043:Collagen Type II; D024081:Collagen Type IX; D024121:Collagen Type X; D016326:Extracellular Matrix Proteins