THE MOUSE AS A MODEL FOR HUMAN GENETICS             
   
   Gene Rinchik and his group in the Biology Division investigate
   mouse-human homologies--mouse genes that are functionally equivalent to
   human genes. "Geneticists have found that the human and mouse genomes
   are very similar," says Rinchik, who has spent the past 13 years working
   with mice. "We have also found that research into the mouse genome can
   answer a lot of questions about the human genome because large blocks of
   genes have been conserved throughout evolution and remain remarkably
   similar."    
   
   Because the mouse is well understood genetically, easy to work with, and
   similar to humans in many ways, including genome size and structure, it
   has become the major model for the study of human genetics and biology.
   Rinchik's group is analyzing about 2 to 3% of the mouse genome. "That
   doesn't seem like much progress," Rinchik says, "but we're also trying
   to determine the function of individual genes in the sequence as we
   go."   
   
   The aim of Rinchik's research is to develop physical, functional, and
   mutation maps for the mouse genome and to use this information to
   predict the functions of the corresponding regions of the human genome.
   "You can't determine this information simply from sequencing the bases
   in a segment of DNA," Rinchik says. "Sequencing can provide important
   information on products of certain genes and reveal their biochemical
   functions, but it does little to predict the function of the gene
   product in the whole organism."               
   
   To determine how a gene functions in the organism as a whole, Rinchik
   uses heritable mutations that alter the quality or quantity of the gene
   product and studies the effect of these alterations on the whole
   organism. One approach to inducing mutations is to use chemical mutagens
   to introduce point mutations along a section of DNA that contains genes
   of interest.        
   
   "We look at the effect of the mutations on the mouse's whole life
   cycle--from fertilization, through fetal development, and into
   reproductive life," says Rinchik. "Unfortunately, because of space
   limitations, we usually can't keep the mice around long enough to study
   late-onset diseases or other conditions related to aging."                 
  
   
   Another approach is to use radiation to delete pieces of DNA from a
   particular region of the mouse genome. This type of mutation is being
   used to study a set of human genetic diseases called contiguous gene
   syndromes. These syndromes are usually attributed to genetic deletion,
   resulting in missing sections of DNA. One of these diseases, known as
   Prader-Willi Syndrome (PWS), occurs in children and is characterized by
   a range of symptoms, such as delayed development. feeding problems in
   infancy, lack of muscle tone, obesity, hypopigmentation, and small hands
   and feet. Any or all of the symptoms may be present in a PWS child.        
               
   
   Rinchik and his group are analyzing deletion in mice having symptoms
   that are somewhat similar to those observed in PWS children. By
   determining the locations of these deletions in mice, researchers hope
   to identify the individual genetic components in the human genome that
   contribute to PWS.        
   
   Continued research into these genomic similarities may eventually permit
   a "surrogate" human genetics to be developed in the mouse, accelerating
   the development of both physical and functional maps of corresponding
   regions of the human genome.
   

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   Date Posted:  1/10/94  (ktb)