Document Type


Patent Number

US Patent 6,194,633

Patent agency

United States Patent and Trademark Office

Publication Date



University of Iowa Research Foundation (Iowa City, IA, US)

Application Number


Date Filed


Total Pages

15 pages


A nonhuman animal having somatic and germ cells in which at least one allele of an endogenous SLP-76 gene is functionally disrupted is provided. The animal may be heterozygous or, more preferably, homozygous for the SLP-76 gene disruption and is preferably a mouse. In homozygous animals, the percentage of peripheral T cells is substantially decreased compared to wildtype animals, whereas the percentage of B cells and macrophages in the periphery is substantially normal, indicating that SLP-76 disruption causes a profound block in T cell development. The animals of the invention can be used, for example, as controls to evaluate the efficacy of SLP-76 inhibitors and to identify disease conditions that can be treated with SLP-76 inhibitors. A transgenic nonhuman animal having a functionally disrupted endogenous SLP-76 gene but which has been reconstituted with an exogenous SLP-76 transgene (e.g., a human SLP-76 gene or a SLP-76 gene whose expression in targeted to a particular cell population) is also provided. An animal that has been reconstituted with a human SLP-76 gene can be used to identify agents that modulate human SLP-76 in vivo. Nucleic acid constructs for functionally disrupting an endogenous SLP-76 gene in a host cell, recombinant vectors including the nucleic acid construct, and host cells into which the nucleic acid construct has been introduced are also encompassed by the invention.