Disease relevance of Fbn2

• Mutation of the gene encoding fibrillin-2 results in syndactyly in mice [1].
• This surprising finding implicates distinct functions for fibrillin-2 in peripheral nerves, because a unique feature in humans and in mice mutant for fibrillin-2 is joint contractures that resolve over time [2].
• Fibrillin-1 mutations result in the pleiotropic manifestations of Marfan syndrome, and fibrillin-2 alterations cause the overlapping phenotype of congenital contractural arachnodactyly [3].

High impact information on Fbn2

• On the other hand, mice double heterozygous for null Fbn2 and Bmp7 alleles display the combined digit phenotype of both nullizygotes [4].
• We also demonstrate that the Fbn2- null mutation is allelic to the recessive shaker-with-syndactyly (sy) locus on chromosome 18 [4].
• To elucidate the contribution of the extracellular microfibril-elastic fiber network to vertebrate organogenesis, we generated fibrillin 2 (Fbn2)-null mice by gene targeting and identified a limb-patterning defect in the form of bilateral syndactyly [4].
• Accordingly, we propose that fibrillin-1 provides mostly force-bearing structural support, whereas fibrillin-2 predominantly regulates the early process of elastic fiber assembly [5].
• Consistent with a specialized function of fibrillin-2, electron microscopy visualized ultrastructurally different microfibrils in Fbn1 null compared with control cell cultures [6].

Biological context of Fbn2

• Of mice and Marfan: genetic linkage analyses of the fibrillin genes, Fbn1 and Fbn2, in the mouse genome [7].
• Synthesis of fibrillin-1 correlates with late morphogenesis and the appearance of well-defined organ structures; fibrillin-2 synthesis, on the other hand, coincides with early morphogenesis and, in particular, with the beginning of elastogenesis [5].
• In all of the genotypes, no differences in fibrillin-2 expression were observed [8].
• These results provide evidence for a cell adhesion function of fibrillin-2 [9].
• In the present study, we identify a new heparin-binding region in fibrillin-2 between exons 18 and 24 [10].

Anatomical context of Fbn2

• Together, these results imply functional interaction between Fbn2-rich microfibrils and BMP-7 signaling [4].
• In postnatal tissues, fibrillin-2 antibodies demonstrated exuberant staining in only one location: peripheral nerves [2].
• The importance of the cell in this process was further underscored by novel data demonstrating that keratinocytes selectively secrete fibrillin-1 into the matrix and not into the medium and can differentiate between fibrillin-1 and fibrillin-2 [11].
• By analyzing a mapping panel of mouse x rodent somatic hybrid cell lines, we have assigned the Fbn-1 gene to mouse chromosome 2 and the Fbn-2 gene to mouse chromosome 18 [12].
• Relaxin regulates fibrillin 2, but not fibrillin 1, mRNA and protein expression by human dermal fibroblasts and murine fetal skin [13].

Other interactions of Fbn2

• Restriction fragment length polymorphisms (RFLPs) between the progenitors of an interspecific backcross involving AEJ/Gn and Mus spretus mice were used to establish the segregation patterns of the murine homologs, Fbn1 and Fbn2, in the backcross progeny [7].
• The results position Fbn2 between the D18Mit35 and Pdgfrb loci in the central region of mouse Chr 18 [7].

Analytical, diagnostic and therapeutic context of Fbn2

• We then sublocalized the fibrillin genes to bands 2F (Fbn-1) and 18D-E1 (Fbn-2) by fluorescence in situ hybridization [12].

References