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M9640698.TXT
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1996-03-04
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Document 0698
DOCN M9640698
TI Cataractogenesis in transgenic mice containing the HIV-1 protease linked
to the lens alpha A-crystallin promoter.
DT 9604
AU Tumminia SJ; Jonak GJ; Focht RJ; Cheng YS; Russell P; Laboratory of
Mechanisms of Ocular Diseases, National Eye; Institute, National
Institues of Health, Bethesda, Maryland; 20892, USA.
SO J Biol Chem. 1996 Jan 5;271(1):425-31. Unique Identifier : AIDSLINE
MED/96132938
AB Several lines of transgenic mice were generated with either active or
inactive forms of the human immunodeficiency virus type 1 (HIV-1)
protease gene under the control of the mouse lens alpha A-crystallin
promoter. Mice bearing the inactive protease coding sequence displayed
no gross abnormalities in the lens, while mice with the active protease
developed time-dependent bilateral cataracts. One line, TG61, developed
cataracts in utero while the second line, TG72, developed cataracts
postnatally. TG61 mice, homozygous for the transgene, developed severe
microphthalmia and were significantly smaller than the control mice at
postnatal day 30. two-dimensional-polyacrylamide gel electrophoresis
analysis of the protein profiles of TG72 and TG61 lenses revealed
extensive modifications in the lens crystallins. Proteolysis in the
homozygous TG72 mouse lenses began at postnatal day 20 with the
disappearance or partial loss of beta B1-, beta B3-, and beta
A3-crystallins and the appearance of crystallin fragments. Protein
leakage and the gradual breakdown of cytoskeletal elements also
occurred. In contrast, the opacification of the homozygous TG61 lenses
appeared to have been influenced by differentiation and developmental
processes. It appears that HIV-1 protease expression activates other
proteases, and these enzymes, in concert with HIV-1 protease, are
responsible for the protein modifications that eventually result in the
opacification of the lens.
DE Amino Acid Sequence Animal Base Sequence Cataract/ETIOLOGY/*GENETICS
Crystallins/*GENETICS Electrophoresis, Gel, Two-Dimensional Homozygote
HIV Protease/*GENETICS Lens, Crystalline/*METABOLISM/PATHOLOGY Mice
Mice, Transgenic Molecular Sequence Data *Promoter Regions (Genetics)
RNA, Messenger/GENETICS/METABOLISM Transgenes JOURNAL ARTICLE
SOURCE: National Library of Medicine. NOTICE: This material may be
protected by Copyright Law (Title 17, U.S.Code).