PUBLICATION
Tissue Distribution and Functional Analysis of Sushi Domain-Containing Protein 4
- Authors
- Tu, Z., Cohen, M., Bu, H., and Lin, F.
- ID
- ZDB-PUB-100330-41
- Date
- 2010
- Source
- The American journal of pathology 176(5): 2378-2384 (Journal)
- Registered Authors
- Keywords
- none
- MeSH Terms
-
- Animals
- Autistic Disorder/metabolism
- Cell Membrane/metabolism*
- Complement C3/chemistry*
- Complement Inactivator Proteins
- Disease Models, Animal
- Enzyme-Linked Immunosorbent Assay
- Facies
- Gene Deletion
- Hernia, Diaphragmatic/metabolism
- Hernias, Diaphragmatic, Congenital
- Humans
- Limb Deformities, Congenital/metabolism
- Membrane Proteins/chemistry
- Membrane Proteins/metabolism*
- Mice
- Mice, Inbred C57BL
- Models, Biological
- Protein Isoforms
- Recombinant Proteins/chemistry
- Zebrafish
- PubMed
- 20348246 Full text @ Am. J. Pathol.
Citation
Tu, Z., Cohen, M., Bu, H., and Lin, F. (2010) Tissue Distribution and Functional Analysis of Sushi Domain-Containing Protein 4. The American journal of pathology. 176(5):2378-2384.
Abstract
Sushi domain-containing protein 4 (SUSD4) was a hypothetical cell surface protein whose tissue distribution and function were completely unknown. However, recent microarray-based studies have identified deletions of SUSD4 gene in patients with autism or Fryns syndrome, both of which are genetic diseases with severe abnormal neurological development and/or functions. In this article, we described the cloning, expression, refolding, tissue distribution, and functional analysis of this novel protein. Using polyclonal antibodies generated by immunizing chickens with the recombinant SUSD4, we found that SUSD4 is detectable in murine brains, eyes, spinal cords, and testis but not other tissues. In brains, SUSD4 is highly expressed in the white matter on oligodendrocytes/axons, and in eyes, it is exclusively expressed on the photoreceptor outer segments. In in vitro complement assays, SUSD4 augments the alternative but not the classical pathway of complement activation at the C3 convertase step. In in vivo studies, knocking down SUSD4 expression in zebrafish markedly increases ratios of mortality and developmental abnormality. These results provide the first insight into the important physiological roles of SUSD4 and could help to better understand the pathogenesis of autism and Fryns syndrome.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping