Cited by 54Connective tissue disorders researchBone and Dental Protein StudiesDermatological and Skeletal Disorders

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

Forlino, Antonella, Tani, Chiara, Rossi, Antonio, Lupi, Anna, Campari, Elena, Gualeni, Benedetta, Bianchi, Laura, Armini, Alessandro +3 more·2007·PROTEOMICS

Abstract

This study used proteomic and transcriptomic techniques to understand the molecular basis of the phenotypic variability in the bone disorder osteogenesis imperfecta (OI). 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 OI murine model BrtlIV, which has either a moderate or a lethal OI 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 αB crystallin was increased in nonlethal mice, suggesting that the intracellular machinery is involved in the modulation of the OI phenotype. Furthermore, in lethal BrtlIV, the increased expression of the cartilaginous proteins Prelp, 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 OI 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.

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Crossref · 10.1002/pmic.200600919

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Authors
Forlino, A., Tani, C., Rossi, A., Lupi, A., Campari, E., Gualeni, B., Bianchi, L., Armini, A., Cetta, G., Bini, L., & Marini, J. C.
Affiliations
  • University of Pavia (IT)
  • University of Siena (IT)
  • National Institutes of Health (US)
Corresponding author
Forlino, Antonella
Venue
PROTEOMICS
Publisher
Wiley
Published
2007-05-22
Volume
7
Issue
11
Pages
1877-1891
ISSN
  • 1615-9853 (ISSN-L)
  • 1615-9861
OpenAlex
W2007055861
Cited by
54
References
48
Citations by year
2026: 1 · 2025: 3 · 2023: 1 · 2022: 3 · 2021: 3 · 2020: 1 · 2019: 2 · 2018: 2 · 2017: 4 · 2016: 1 · 2015: 4 · 2014: 1 · 2013: 6 · 2012: 4
FWCI
2.87
Type
journal article
Language
en
Open access
closed
Locations
  • PROTEOMICS (publishedVersion)
  • PubMed (publishedVersion)
  • Use Siena air (University of Siena) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
  • Health Sciences › Medicine › Rheumatology › Bone and Dental Protein Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Dermatological and Skeletal Disorders
Keywords
osteogenesis imperfecta, phenotypic variability, calvarial bone, differentially expressed proteins, GADD153, endoplasmic reticulum stress, alphaB-crystallin, molecular chaperones, BMP6, BMP-7, PRELP, extracellular matrix, skeletal development
MeSH terms
Animals, Bone and Bones, Disease Models, Animal, Genes, Lethal, Genetic Markers, Osteogenesis Imperfecta, Phenotype, Genetic Variation, Blotting, Western, Electrophoresis, Gel, Two-Dimensional, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Amino Acid Substitution, Reverse Transcriptase Polymerase Chain Reaction, Collagen Type I, Microarray Analysis, Mice, Transcription Factor CHOP

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