       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).

