title: CCM2 expression parallels that of CCM1.
abstract: OBJECTIVE
  Mutations in CCM2 (MGC4607 or malcavernin) cause familial cerebral cavernous malformation (CCM), an autosomal dominant neurovascular disease. Both the function of this molecule and the pathogenesis of the disease remain elusive.
  
  
  METHODS
  We analyzed the mRNA expression of Ccm1 and Ccm2 in the embryonic and postnatal mouse brain by in situ hybridization. Subsequently, we generated CCM2-specific polyclonal antibodies and tested their specificity using transient transfection experiments in various cell lines. We then investigated CCM2 protein expression in cerebral and extracerebral tissues by Western blot analysis as well as immunohistochemistry and compared these results with CCM1 (KRIT1) protein expression.
  
  
  RESULTS
  In situ analysis shows similar temporal and spatial expression patterns for Ccm1 and Ccm2, although Ccm1 expression appears more widespread. Immunohistochemical analysis shows that CCM2 is expressed in various human organs, most noticeably in the arterial vascular endothelium. As is the case with CCM1, CCM2 is not expressed in other vascular wall elements such as smooth muscle cells or the venous circulation. Within cerebral tissue, it is also expressed in pyramidal neurons, astrocytes, and their foot processes. In extracerebral tissues, CCM2 is present in various epithelial cells necessary for blood-organ barrier formation.
  
  
  CONCLUSIONS
  CCM1 and CCM2 have similar expression patterns during development and postnatally thereafter. Given the fact that the disease phenotypes caused by mutations in either gene are clinically and pathologically indistinguishable, the significant overlap in expression pattern supports the hypothesis that both molecules are involved in the same pathway important for central nervous system vascular development.
authors.affiliation: Department of Neurosurgery, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: Askin
authors.initials: A
authors.lastname: Seker
authors.forename: Katie L
authors.initials: KL
authors.lastname: Pricola
authors.forename: Bulent
authors.initials: B
authors.lastname: Guclu
authors.forename: Ali K
authors.initials: AK
authors.lastname: Ozturk
authors.forename: Angeliki
authors.initials: A
authors.lastname: Louvi
authors.forename: Murat
authors.initials: M
authors.lastname: Gunel
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000196:embryology* / Q000473:pathology; D019556:COS Cells; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D002478:Cells, Cultured; D002490:Central Nervous System / Q000473:pathology; D002540:Cerebral Cortex / Q000473:pathology; D002522:Chlorocebus aethiops; D004730:Endothelium, Vascular / Q000166:cytology / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D000075927:KRIT1 Protein; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009130:Muscle, Smooth / Q000473:pathology; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D020798:Two-Hybrid System Techniques; D014471:Umbilical Veins / Q000166:cytology
chemical_list: C502544:CCM2 protein, human; D002352:Carrier Proteins; D000075927:KRIT1 Protein; C107928:KRIT1 protein, human; C491535:Krit1 protein, mouse; D008869:Microtubule-Associated Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger