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Characterization of CI1L gene expression on human tissues: identificaiton of CR1L-2, a two SCR transcript from human fetal liver and bone marrow

Irshaid, Fawzi Irshaid

Abstract Details

2005, Doctor of Philosophy, Ohio State University, Molecular, Cellular, and Developmental Biology.
CR1-like (CR1L) is a genetic element, identified from human genomic clones, with high homology to complement receptor type one (CR1). Though CR1L is expressed in most non-human primates as the immune adherence receptor, little is known of human CR1L expression. Previous studies have identified in human primary lymphoid tissue a CR1L transcript, by RT-PCR, containing a sequence for 8 short consensus repeats (SCRs). However, no mRNA (by northern) or natively expressed protein has been found. Thus, the purpose of this study was to further characterize the expression of human CR1L. In this study, evidence was found for two novel human transcripts by northern blot analysis that hybridized with probes derived from the human CR1L transcript. The first was a 1.2 kb transcript identified in human pancreas. However, additional attempts to identify this transcript, or its protein product, using RT-PCR, RACE, cDNA libraries and western blots were unsuccessful, suggesting that the 1.2 kb transcript appears to be unrelated to CR1/CR1L. The second novel transcript of 0.7 kb, was also revealed through northern blot analysis, with predominant expression occurring in human fetal liver and bone marrow. This transcript, which we’ve termed CR1L-2, was fully characterized by RT-PCR and additional northern blot analysis, and contains encoding sequence for a signal peptide, CR1L SCRs 1 and 2 and a hydrophobic C-terminal predictive of GPI-linkage. To date, no immunologic reagents with specificity towards CR1L-2 are available, thus preventing the demonstration of native protein expression of this abundant transcript. Expression of recombinant CR1L-2, with C-terminal epitopes, suggests a molecular weight of 23 kDa for the mature CR1L-2 protein. Pilot experiments into the function of this protein suggest that it binds the complement fragment C4d, but not C4b, C3b or C3bi. The predominant expression in fetal liver and bone marrow suggests that CR1L-2 plays a role in early lymphogeneisis or hematopoiesis. Specifically, as a potential C4d binding protein, CR1L-2 could modulate the effect that C4 has on the immune response, especially with regards to the developing B cell repertoire and to C4-based susceptibility to autoimmune diseases such as systemic lupus erythematosus.
Dr. Daniel Birmingham, (Advisor)
Dr. Chack Yu (Other)
Dr. Douglas Kniss (Other)
Dr. Arthur Strauch (Other)
124 p.

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Citations

  • Irshaid, F. I. (2005). Characterization of CI1L gene expression on human tissues: identificaiton of CR1L-2, a two SCR transcript from human fetal liver and bone marrow [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111530577

    APA Style (7th edition)

  • Irshaid, Fawzi. Characterization of CI1L gene expression on human tissues: identificaiton of CR1L-2, a two SCR transcript from human fetal liver and bone marrow. 2005. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1111530577.

    MLA Style (8th edition)

  • Irshaid, Fawzi. "Characterization of CI1L gene expression on human tissues: identificaiton of CR1L-2, a two SCR transcript from human fetal liver and bone marrow." Doctoral dissertation, Ohio State University, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=osu1111530577

    Chicago Manual of Style (17th edition)