The mgΔlpn mouse model for Marfan syndrome recapitulates the ocular phenotypes of the disease.

PURPOSE: Fibrillin-1 and -2 are major components of tissue microfibrils that compose the ciliary zonule and cornea. While mutations in human fibrillin-1 lead to ectopia lentis, a major manifestation of Marfan syndrome (MFS), in mice fibrillin-2 can compensate for reduced/lack of fibrillin-1 and maintain the integrity of ocular structures. Here we examine the consequences of a heterozygous dominant-negative mutation in the Fbn1 gene in the ocular system of the mgΔlpn mouse model for MFS. METHODS: Eyes from mgΔlpn and wild-type mice at 3 and 6 months of age were analyzed by histology. The ciliary zonule was analyzed by scanning electron microscopy (SEM) and immunofluorescence. RESULTS: Mutant mice presented a significantly larger distance of the ciliary body to the lens at 3 and 6 months of age when compared to wild-type, and ectopia lentis. Immunofluorescence and SEM corroborated those findings in MFS mice, revealing a disorganized mesh of microfibrils on the floor of the ciliary body. Moreover, mutant mice also had a larger volume of the anterior chamber, possibly due to excess aqueous humor. Finally, losartan treatment had limited efficacy in improving ocular phenotypes. CONCLUSIONS: In contrast with null or hypomorphic mutations, expression of a dominant-negative form of fibrillin-1 leads to disruption of microfibrils in the zonule of mice. This in turn causes lens dislocation and enlargement of the anterior chamber. Therefore, heterozygous mgΔlpn mice recapitulate the major ocular phenotypes of MFS and can be instrumental in understanding the development of the disease.

The tooth as a monitor of cholestatic liver disease in rats.

OBJECTIVE: Measure, noninvasively, the deposition of bilirubin in the tooth by using DIAGNOdent and correlate it to liver dysfunction. STUDY DESIGN: After confirming the capacity of DIAGNOdent to measure varying bile concentrations in plaster blocks, a cholestatic liver disease model was studied to detect increasing bilirubin impregnation in the teeth of rats. Wistar-EPM rats (n = 50) were divided into three groups: (1) BDL: rats submitted to bile duct ligation (BDL); (2) Naïve: rats without procedure; and (3) Sham: rats submitted to laparotomy without BDL (n = 10/period/group). The rats' teeth were monitored with the use of DIAGNOdent before the procedure and at days 10 and 50 following surgery. Serum bilirubin was also monitored. RESULTS: Tests in vitro showed that DIAGNOdent detected bile in plaster blocks according to its concentration. BDL promoted progressive liver dysfunction, with death occurring approximately 50 days later. DIAGNOdent values obtained on teeth showed correlation with the progression of serum hyperbilirubinemia. CONCLUSIONS: The tooth was found to be a good tissue for noninvasively monitoring the progression of bilirubinemia in cholestatic liver disease in rats by using DIAGNOdent.