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

Submitted July 3, 2002
Accepted September 9, 2002
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*
Sidney Kimmel Cancer Center, San Diego, CA, USA
* Corresponding author; email: braschke{at}skcc.org.
Transgenic mice have been generated which 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 SCID-associated defects and represents a potential route to a gene therapy for human CD45-deficent SCID.

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