Korean J Orthod.  2003 Dec;33(6):485-497.

Generation of a transgenic mouse model to study cranial suture development; Apert syndrome

• Lee KJ
• Ratisoontorn C
• Baik HS
• Park YC
• Park KK
• Nah HD

Abstract

The form and function of the craniofacial structure critically depend on genetic information. With recent advances in the molecular technology, genes that are important for normal growth and morphogenesis of the craniofacial skeleton are being rapidly uncovered, shaping up modern craniofacial biology. One of them is fibroblast growth factor receptor 2 (FGFR2). Specific point mutations in the FGFR2 gene have been linked to Apert syndrome, which is characterized by premature closure of cranial sutures and craniofacial anomalies as well as limb deformities. To study pathogenic mechanisms underlying craniosynostosis phenotype of Apert syndrome, we used a transgenic approach; an FGFR2 minigene construct containing an Apert mutation (a point mutation that substitute proline at the position 253 to arginine; P253R) was introduced into fertilized mouse germ cells by DNA microinjection. The injected cells were then allowed to develop into transgenic mice. We used a bone-specific promoter (a DNA fragment from the type I collagen gene) to confine the expression of mutant FGFR2 gene to the bone tissue, and asked whether expression of mutant FGFR2 in bone is sufficient to cause the craniosynostosis phenotype in mice. Initial characterization of these mice shows prematurely closed cranial sutures with facial deformities expected from Apert patients. We also demonstrate that the transgene produces mutant FGFR2 protein with increased functional activities. Having this useful mouse model, we now can ask questions regarding the role of FGFR2 in normal and abnormal development of cranial bones and sutures.

Keyword

FGFR2; Apert syndrome; Transgenic mice; Bone-specific promoter

MeSH Terms

Acrocephalosyndactylia*
Animals
Arginine
Biology
Bone and Bones
Collagen Type I
Congenital Abnormalities
Cranial Sutures*
Craniosynostoses
DNA
Extremities
Germ Cells
Humans
Mice
Mice, Transgenic*
Microinjections
Morphogenesis
Phenotype
Point Mutation
Proline
Receptor, Fibroblast Growth Factor, Type 2
Skeleton
Sutures
Transgenes
Arginine
Collagen Type I
DNA
Proline
Receptor, Fibroblast Growth Factor, Type 2