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 Prepublished online as a Blood First Edition Paper on September 19, 2002; DOI 10.1182/blood-2002-07-1969.

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Blood, 1 February 2003, Vol. 101, No. 3, pp. 849-855

GENE THERAPY

A CD45 minigene restores regulated isoform expression and immune function in CD45-deficient mice: therapeutic implications for human CD45-null severe combined immunodeficiency

Elizabeth L. Virts, Oscar Diago, and William C. Raschke

From the Sidney Kimmel Cancer Center, San Diego, CA.

Transgenic mice have been generated that carry a CD45 minigene under control of the human leukocyte function-associated antigen (LFA-1, CD11a) promoter. CD45-null mice carrying the transgene exhibit the lymphocyte lineage-specific isoform expression patterns of wild-type mice. Furthermore, these mice have normal thymocyte development and peripheral T-cell numbers. The proliferative ability of T cells in response to mitogens and antigen also is regained, as is B-cell responsiveness to anti-IgM. The antibody response to antigen is also restored and is similar to that of normal mice. Therefore, introduction of a functional CD45 minigene is sufficient to overcome the principal severe combined immunodeficiency (SCID)-associated defects and represents a potential route to a gene therapy for human CD45-deficent SCID.

© 2003 by The American Society of Hematology.
 

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