       Document 0268
 DOCN  M95A0268
 TI    Increased central nervous system production of extracellular matrix
       components and development of hydrocephalus in transgenic mice
       overexpressing transforming growth factor-beta 1.
 DT    9510
 AU    Wyss-Coray T; Feng L; Masliah E; Ruppe MD; Lee HS; Toggas SM;
       Rockenstein EM; Mucke L; Department of Neuropharmacology, Scripps
       Research Institute,; California, USA.
 SO    Am J Pathol. 1995 Jul;147(1):53-67. Unique Identifier : AIDSLINE
       MED/95328623
 AB    A number of important neurological diseases, including HIV-1
       encephalitis, Alzheimer's disease, and brain trauma, are associated with
       increased cerebral expression of the multifunctional cytokine
       transforming growth factor-beta 1 (TGF-beta 1). To determine whether
       overexpression of TGF-beta 1 within the central nervous system (CNS) can
       contribute to the development of neuropathological alterations, a
       bioactive form of TGF-beta 1 was expressed in astrocytes of transgenic
       mice. Transgenic mice with high levels of cerebral TGF-beta 1 expression
       developed a severe communicating hydrocephalus, seizures, motor
       incoordination, and early runting. While unmanipulated heterozygous
       transgenic mice from a low expressor line showed no such alterations,
       increasing TGF-beta 1 expression in this line by injury-induced
       astroglial activation or generation of homozygous offspring did result
       in the abnormal phenotype. Notably, astroglial overexpression of
       TGF-beta 1 consistently induced a strong upmodulation of the
       extracellular matrix proteins laminin and fibronectin in the CNS,
       particularly in the vicinity of TGF-beta 1-expressing perivascular
       astrocytes, but was not associated with obvious CNS infiltration by
       hematogenous cells. While low levels of extracellular matrix protein
       expression may assist in CNS wound repair and regeneration, excessive
       extracellular matrix deposition could result in the development of
       hydrocephalus. As an effective inducer of extracellular matrix
       components, TGF-beta 1 may also contribute to the development of other
       neuropathological alterations, eg, the formation of amyloid plaques in
       Alzheimer's disease.
 DE    Animal  Astrocytes/METABOLISM/PATHOLOGY  Brain/*METABOLISM/PATHOLOGY
       Extracellular Matrix Proteins/*BIOSYNTHESIS  Gene Expression Regulation
       Glial Fibrillary Acidic Protein/GENETICS
       Hydrocephalus/*ETIOLOGY/PATHOLOGY  Immunoblotting  Immunohistochemistry
       Mice  Mice, Inbred BALB C  Mice, Transgenic  Microscopy, Confocal  RNA,
       Messenger/BIOSYNTHESIS  Seizures/ETIOLOGY/PATHOLOGY  Support, Non-U.S.
       Gov't  Support, U.S. Gov't, P.H.S.  Transforming Growth Factor
       beta/*BIOSYNTHESIS/GENETICS  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

