Differential expression of both extracellular and intracellular proteins is involved in the lethal or nonlethal phenotypic variation of BrtIIV, a murine model for osteogenesis imperfecta

作者：Forlino Antonella^*; Tani Chiara; Rossi Antonio; Lupi Anna; Campari Elena; Gualeni Benedetta; Bianchi Laura; Armini Alessandro; Cetta Giuseppe; Bini Luca; Marini Joan C

来源：Proteomics, 2007, 7(11): 1877-1891.

DOI：10.1002/pmic.200600919

• 2-DE
• allele specific real-time PCR
• microarray
• osteogenesis imperfecta
• phenotypic variability

This study used proteomic and transcriptomic techniques to understand the molecular basis of the phenotypic variability in the bone disorder osteogenesis imperfecta (01). Calvarial bone mRNA expression was evaluated by microarray, real-time, and comparative RT-PCR and the bone proteome profile was analyzed by 2-DE, MS, and immunoblotting in the 01 murine model BrtlIV, which has either a moderate or a lethal 01 outcome. Differential expression analysis showed significant changes for eight proteins. The expression of the ER stress-related protein Gadd153 was increased in lethal mice, whereas expression of the chaperone alpha B crystallin was increased in nonlethal mice, suggesting that the intracellular machinery is involved in the modulation of the 01 phenotype. Furthermore, in lethal BrdlIV, the increased expression of the cartilaginous proteins Pre1p, Bmp6, and Bmp7 and the lower expression of the bone matrix proteins matrilin 4, microfibril-associated glycoprotein 2, and thrombospondin 3 revealed that both a delay in skeletal development and an alteration in extracellular matrix composition influence 01 outcomes. Differentially expressed proteins identified in this model offer a starting point for elucidating the molecular basis of phenotypic variability, a characteristic common to many genetic disorders. The first reference 2-DE map for murine calvarial tissue is also reported.

• 出版日期2007-6