title: A Novel Mgp-Cre Knock-In Mouse Reveals an Anticalcification/Antistiffness Candidate Gene in the Trabecular Meshwork and Peripapillary Scleral Region.
abstract: OBJECTIVE
  Soft tissue calcification is a pathological condition. Matrix Gla (MGP) is a potent mineralization inhibitor secreted by cartilage chondrocytes and arteries' vascular smooth muscle cells. Mgp knock-out mice die at 6 weeks due to massive arterial calcification. Arterial calcification results in arterial stiffness and higher systolic blood pressure. Intriguingly, MGP was highly abundant in trabecular meshwork (TM). Because tissue stiffness is relevant to glaucoma, we investigated which additional eye tissues use Mgp's function using knock-in mice.
  
  
  METHODS
  An Mgp-Cre-recombinase coding sequence (Cre) knock-in mouse, containing Mgp DNA plus an internal ribosomal entry site (IRES)-Cre-cassette was generated by homologous recombination. Founders were crossed with Cre-mediated reporter mouse R26R-lacZ. Their offspring expresses lacZ where Mgp is transcribed. Eyes from MgpCre/+;R26RlacZ/+ (Mgp-lacZ knock-in) and controls, 1 to 8 months were assayed for β-gal enzyme histochemistry.
  
  
  RESULTS
  As expected, Mgp-lacZ knock-in's TM was intensely blue. In addition, this mouse revealed high specific expression in the sclera, particularly in the peripapillary scleral region (ppSC). Ciliary muscle and sclera above the TM were also positive. Scleral staining was located immediately underneath the choroid (chondrocyte layer), began midsclera and was remarkably high in the ppSC. Cornea, iris, lens, ciliary body, and retina were negative. All mice exhibited similar staining patterns. All controls were negative.
  
  
  CONCLUSIONS
  Matrix Gla's restricted expression to glaucoma-associated tissues from anterior and posterior segments suggests its involvement in the development of the disease. Matrix Gla's anticalcification/antistiffness properties in the vascular tissue, together with its high TM and ppCS expression, place this gene as a strong candidate for TM's softness and sclera's stiffness regulation in glaucoma.
authors.forename: Teresa
authors.initials: T
authors.lastname: Borrás
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Smith
authors.forename: LaKisha K
authors.initials: LK
authors.lastname: Buie
mesh_terms: D000818:Animals; D002114:Calcinosis / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004247:DNA / Q000235:genetics*; D004195:Disease Models, Animal; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D005838:Genotype; D005901:Glaucoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D012590:Sclera / Q000378:metabolism* / Q000473:pathology; D014129:Trabecular Meshwork / Q000378:metabolism* / Q000473:pathology; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D004247:DNA; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein