The 40-kb region downstream of the most 3' immunoglobulin (Ig) heavy chain constant region gene (Calpha) contains a series of transcriptional enhancers speculated to play a role in Ig heavy chain class switch recombination (CSR). To elucidate the function of this putative CSR regulatory region, we generated mice with germline mutations in which one or the other of the two most 5' enhancers in t...

OBJECTIVE The goal of this study was to determine the utility of adeno-associated virus (AAV) vectors for anti-angiogenic gene therapy in a mouse model of collagen-induced arthritis (CIA). METHODS CIA mice were generated by immunization with bovine type-II collagen and Freund's complete adjuvant. AAV vectors containing angiostatin and enhanced green fluorescent protein (eGFP) expression units...

Bcl-2 has been shown to inhibit apoptosis induced by several anticancer agents and to cause a dissociation between etoposide (VP-lot-induced protein-cross-linked DNA strand breaks and VP-16-induced cell death. We suggested previously that VP-16-induced cytotoxicity is mediated by a series of events leading from cleavable complex formation to aberrant UNA recombination, as measured by sister chr...

A Moloney murine leukemia virus based retroviral vector was used to transfer the bacterial neomycin resistance gene (neoR) into feline hematopoietic cells. We reconstituted four cats that had been lethally irradiated with autologous bone marrow that had been infected with the N2 or SAX retroviral vector. Bone marrow cells from all four cats expressed the neoR gene 30 days posttransplant and thr...

We investigated the tumorigenicity and immunogenicity of tumor cells transfected with an allogeneic class I major histocompatibility complex gene. A single clone (3LL/3) from a Lewis lung carcinoma in the C57BL/6 strain (H-2b) was cotransfected with a BALB/c genomic clone containing an H-2Ld gene and a bacterial neo gene conferring resistance to G418. Three Ld-positive, three Ld-negative, and t...

This paper presents an algorithm for developing models under Dempster-Shafer theory of belief functions for categorical and 'uncertain' logical relationships among binary variables. We illustrate the use of the algorithm by developing belief-function representations of the following categorical relationships: 'AND', 'OR', 'Exclusive OR (EOR)' and 'Not Exclusive OR (NEOR)', and 'AND-NEOR' and of...

The adenomatous polyposis coli (APC) gene, whose mutations are responsible for familial adenomatous polyposis, is a major negative controller of the Wnt/beta-catenin pathway. To investigate the dose-dependent effects of APC protein in suppressing intestinal tumorigenesis, we constructed mutant mice carrying hypomorphic Apc alleles Apc(neoR) and Apc(neoF) whose expression levels were reduced to ...

Recombinant protein production coopts the host cell machinery to provide high protein yields of industrial enzymes or biotherapeutics. However, since protein translation is energetically expensive and tightly controlled, it is unclear if highly expressed recombinant genes are translated as efficiently as host genes. Furthermore, it is unclear how the high expression impacts global translation. ...

Primitive hematopoietic progenitor cells (HPCs) are potential targets for treatment of numerous hematopoietic diseases using retroviral-mediated gene transfer (RMGT). To achieve high efficiency of gene transfer into primitive HPCs, a delicate balance between cellular activation and proliferation and maintenance of hematopoietic potential must be established. We have demonstrated that a subpopul...