- CD4 is a T cell differentiation antigen expressed as a transmembrane surface glycoprotein on thymocytes and mature T lymphocytes. The Cd4 Knockout/hCD4 mouse model expresses a dysfunctional variant of the human CD4 molecule on a murine Cd4 knockout background. The human CD4 transgene has a point mutation which disrupts interaction between the CD4 molecule and MHC class II molecules. The hCD4 transgene is overexpressed on lymphocytes in the thymus, spleen, and peripheral blood. However, the number of mature CD4+ T cells and Th cell function are decreased in comparison with wild type mice, providing evidence for the role of MHC class II-CD4 interaction in the maturation of the CD4 T cell lineage.
- The mutant hCD4 transgene also leads to an altered TCR repertoire, with different Vα and Vβ gene usage than is seen in wild type mice.
- This model can be used to study the development of the CD4 T cell lineage and to delineate the role of MHC class II interaction in T cell function and formation of the TCR repertoire.
Genetic Background: C57BL/6
Origin: Dr. Toshika Sakihama and colleagues in the Ellis Reinherz laboratory at Dana-Farber Cancer Institute made this human CD4 transgenic model on the murine Cd4 knockout background. A human CD4 molecule with a point mutation (Phe to Ile at amino acid residue 43) in the C’ strand residue of domain 1 (a region essential for binding MHC class II molecules) was generated by site-directed mutagenesis. The transgene was injected into fertilized eggs of mixed stock, and resultant transgene-positive mice were backcrossed to Cd4 knockout mice (Taconic model #1055) for 14 generations. The Cd4/hCD4 mice were received at Taconic in September 1999 and embryo transfer derived. The colony was maintained by breeding homozygous/hemizygous Cd4/hCD4 mice with homozygous Cd4 knockout mice to produce homozygous/hemizygous Cd4/hCD4 mice.
Sakihama T, Hunsicker ME, Hussey RE, Reinherz EL; Human CD4 residue Phe 43 is critical for repertoire development and maturation of MHC class II restricted CD4 single-positive T lineage cells in vivo
; Eur J Immunol 2000 30:279-290
. Note: The transgene with the point mutation (F43I) described in this publication is inserted on the X chromosome. The line received at Taconic has the same mutant hCD4, however, it is not linked to the X chromosome. The phenotype, class II MHC restriction and dependence are the same as described in the publication.