title: Immunohistochemical and genetic analysis of mandibular cysts in heterozygous ptc knockout mice.
abstract: BACKGROUND
  Alterations of human patched (ptc) homolog have been proven to be responsible for basal cell nevus syndrome (BCNS). Mandibular cysts in heterozygous ptc knockout mouse (ptc+/- mouse) were microradiologically, histologically, immunohistochemically, and genetically examined to investigate the possible role of the ptc gene and its associates in the jaw cysts.
  
  
  METHODS
  The mandibular bones were prepared from 63 ptc+/- mice and 6 ptc+/+ mice. Soft X-ray radiographs and histological sections were examined for detection of the presence of mandibular cysts. The mandibular cysts were immunohistochemically investigated using anti-ptc, shh, and smo antibodies. PCR analysis of loss of heterozygosity (LOH) of ptc was performed in genomic DNA from the mandibular cysts.
  
  
  RESULTS
  Six ptc+/+ mice showed no pathologic change in any examinations. Microradiologically, ptc+/- mice did not show any apparent lesion. Mandibular cysts were often multiple, and were histologically detected in the alveolar bones or periodontal ligaments of the molars in 16 (25.4%) ptc+/- mice. The mandibular cysts were lined by thin parakeratotic stratified squamous epithelium and contained keratinized materials. Immunohistochemical examination showed sonic hedgehog (shh) protein mainly in cyst lining epithelium, and ptc and smoothened (smo) proteins in cyst lining epithelium, and surrounding fibrous connective tissue. Expression of ptc protein in the cyst lining epithelium tended to be weak as compared with incisor enamel organs and gingival stratified squamous epithelium. LOH of the ptc gene couldn't be found in lining epithelium of mandibular cysts in any ptc+/- mice.
  
  
  CONCLUSIONS
  Ptc+/- mouse is a useful model of BCNS from the standpoint of occurrence of jaw cysts, and downregulation of ptc protein in cyst lining epithelium caused by gene targeting would be associated with formation of jaw cysts in ptc+/- mice.
authors.affiliation: Department of Oral Medicine and Bioregulation, Tohoku University Graduate School of Dentistry, Sendai, Japan.
authors.forename: Kenji
authors.initials: K
authors.lastname: Kimi
authors.forename: Kousuke
authors.initials: K
authors.lastname: Ohki
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Kumamoto
authors.forename: Mari
authors.initials: M
authors.lastname: Kondo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Akira
authors.initials: A
authors.lastname: Tanigami
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Ooya
mesh_terms: D000818:Animals; D001478:Basal Cell Nevus Syndrome / Q000235:genetics; D005260:Female; D015870:Gene Expression; D053823:Hedgehog Proteins; D006579:Heterozygote; D007150:Immunohistochemistry; D047908:Intracellular Signaling Peptides and Proteins; D019656:Loss of Heterozygosity; D008297:Male; D008336:Mandibular Diseases / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000096:biosynthesis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D009807:Odontogenic Cysts / Q000235:genetics / Q000378:metabolism*; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010519:Periodontium / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011956:Receptors, Cell Surface / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled; D000072086:Smoothened Receptor; D014083:Tooth Germ / Q000378:metabolism; D015534:Trans-Activators / Q000096:biosynthesis
chemical_list: D053823:Hedgehog Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; C000606236:PTCH1 protein, human; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; C000606240:Ptch1 protein, mouse; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C509239:SHH protein, human; C491022:Smo protein, mouse; D000072086:Smoothened Receptor; D015534:Trans-Activators