Phenotypic and molecular analyses of A/WySn mice.
OBJECTIVE
Since its first description, the A strain of mice have been utilized extensively as models to study the processes involved in clefting of the midfacial region. Of the A substrains, the A/WySn has a spontaneous rate of clefting of the lip of about 20% to 30%. The A/WySn mouse model was utilized in this study to analyze and compare the phenotypic and molecular changes in the midfacial region of embryos with and without cleft.


RESULTS
Scanning electron microscopy and skeletal and cartilage preparations of newborn A/WySn pups showed the presence of bilateral and unilateral clefts of the lips and the disruption of the skeletal and cartilaginous components of the mice with clefts of the lip. The expression of the msx1 homeobox gene was analyzed by whole mount in situ hybridization of A/WySn embryos at different stages of midfacial development. The results showed that there was misregulation of the expression of the msx1 gene in embryos with cleft, with a persistence of expression in the distal growing tips of the midfacial processes and in areas that have fused in normal embryos without cleft.


CONCLUSIONS
Although the genetic defect in A/WySn mice is not known, a possible candidate gene has been mapped to a corresponding human chromosome carrying retinoic acid receptor alpha, and there exists a possibility that msx1 is in the same genetic pathway affected by the mutation of the gene in A/WySn.
Gong
S G
SG
Department of Orthodontics and Pediatric Dentistry, School of Dentistry, University of Michigan, 1011 North University Avenue, Ann Arbor, MI 48109-1078, USA. sggong@umich.edu
D000818:Animals; D002356:Cartilage / Q000196:embryology / Q000473:pathology; D002874:Chromosome Mapping; D002971:Cleft Lip / Q000196:embryology / Q000235:genetics* / Q000473:pathology; D004195:Disease Models, Animal; D005147:Facial Bones / Q000196:embryology / Q000473:pathology; D018507:Gene Expression Regulation, Developmental; D005801:Genes, Homeobox / Q000235:genetics; D005865:Gestational Age; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017403:In Situ Hybridization; D051957:MSX1 Transcription Factor; D008437:Maxilla / Q000196:embryology / Q000473:pathology; D051379:Mice; D008805:Mice, Inbred A; D008815:Mice, Inbred Strains; D008855:Microscopy, Electron, Scanning; D009154:Mutation / Q000235:genetics; D009666:Nose / Q000196:embryology / Q000473:pathology; D010159:Palate / Q000196:embryology / Q000473:pathology; D010641:Phenotype; D018168:Receptors, Retinoic Acid / Q000235:genetics; D000072482:Retinoic Acid Receptor alpha; D019291:Skull Base / Q000196:embryology / Q000473:pathology; D014157:Transcription Factors
D018398:Homeodomain Proteins; D051957:MSX1 Transcription Factor; C000607071:RARA protein, human; C000607072:Rara protein, mouse; D018168:Receptors, Retinoic Acid; D000072482:Retinoic Acid Receptor alpha; D014157:Transcription Factors