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Mutations in Col4a1 cause perinatal cerebral hemorrhage and porencephaly.
- Source :
-
Science (New York, N.Y.) [Science] 2005 May 20; Vol. 308 (5725), pp. 1167-71. - Publication Year :
- 2005
-
Abstract
- Porencephaly is a rare neurological disease, typically manifest in infants, which is characterized by the existence of degenerative cavities in the brain. To investigate the molecular pathogenesis of porencephaly, we studied a mouse mutant that develops porencephaly secondary to focal disruptions of vascular basement membranes. Half of the mutant mice died with cerebral hemorrhage within a day of birth, and approximately 18% of survivors had porencephaly. We show that vascular defects are caused by a semidominant mutation in the procollagen type IV alpha 1 gene (Col4a1) in mice, which inhibits the secretion of mutant and normal type IV collagen. We also show that COL4A1 mutations segregate with porencephaly in human families. Because not all mutant mice develop porencephaly, we propose that Col4a1 mutations conspire with environmental trauma in causing the disease.
- Subjects :
- Alleles
Amino Acid Sequence
Amino Acid Substitution
Animals
Animals, Newborn
Basement Membrane embryology
Basement Membrane metabolism
Basement Membrane pathology
Brain blood supply
Brain embryology
Brain Diseases etiology
Brain Diseases pathology
Cerebral Hemorrhage etiology
Cerebral Hemorrhage pathology
Chromosome Mapping
Collagen Type IV chemistry
Collagen Type IV metabolism
Endoderm metabolism
Heterozygote
Humans
Mice
Protein Structure, Tertiary
Brain pathology
Brain Diseases genetics
Cerebral Hemorrhage genetics
Collagen Type IV genetics
Mutation
Subjects
Details
- Language :
- English
- ISSN :
- 1095-9203
- Volume :
- 308
- Issue :
- 5725
- Database :
- MEDLINE
- Journal :
- Science (New York, N.Y.)
- Publication Type :
- Academic Journal
- Accession number :
- 15905400
- Full Text :
- https://doi.org/10.1126/science.1109418