Role of COL4A1 in Small-Vessel Disease and Hemorrhagic Stroke
Douglas B. Gould, Ph.D., F. Campbell Phalan, B.A., Saskia E. van Mil, M.Sc., John P. Sundberg, Ph.D., Katayoun Vahedi, M.D., Pascale Massin, M.D., Marie Germaine Bousser, M.D., Peter Heutink, Ph.D., Jeffrey H. Miner, Ph.D., Elisabeth Tournier-Lasserve, M.D., and Simon W.M. John, Ph.D.
Small-vessel diseases of the brain underlie 20 to 30 percentof ischemic strokes and a larger proportion of intracerebralhemorrhages. In this report, we show that a mutation in themouse Col4a1 gene, encoding procollagen type IV 1, predisposesboth newborn and adult mice to intracerebral hemorrhage. Surgicaldelivery of mutant mice alleviated birth-associated trauma andhemorrhage. We identified a COL4A1 mutation in a human familywith small-vessel disease. We concluded that mutation of COL4A1may cause a spectrum of cerebrovascular phenotypes and thatpersons with COL4A1 mutations may be predisposed to hemorrhage,especially after environmental stress.
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From the Howard Hughes Medical Institute (D.B.G., F.C.P., S.W.M.J.) and the Jackson Laboratory (D.B.G., F.C.P., J.P.S., S.W.M.J.) — both in Bar Harbor, Me.; the Department of Human Genetics, Section of Medical Genomics, VU University Medical Center, and the Center for Neurogenomics and Cognitive Research, VU University and VU University Medical Center, Amsterdam (S.E.M., P.H.); Service de Neurologie (K.V., M.G.B.) and Service d'Ophtalmologie (P.M.), Assistance Publique des Hôpitaux de Paris, Hôpital Lariboisière, Paris; INSERM Unité 740 and Laboratoire de Génétique, Assistance Publique des Hôpitaux de Paris, Paris (M.G.B., E.T.-L.); the Renal Division, Washington University School of Medicine, St. Louis (J.H.M.); and the Department of Ophthalmology, Tufts University School of Medicine, Boston (S.W.M.J.).
Address reprint requests to Dr. John at the Jackson Laboratory, 600 Main St., Bar Harbor, ME 04609, or at swmj{at}jax.org.
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1, predisposes both newborn and adult mice to intracerebral hemorrhage. Surgical delivery of mutant mice alleviated birth-associated trauma and hemorrhage. We identified a COL4A1 mutation in a human family with small-vessel disease. We concluded that mutation of COL4A1 may cause a spectrum of cerebrovascular phenotypes and that persons with COL4A1 mutations may be predisposed to hemorrhage, especially after environmental stress. 
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