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Molecular basis for complement component 6 (C6) deficiency in rats and mice.

Abstract：

:Complement component C6 is a part of the lytic membrane attack complex formed during complement activation. Animal modeling to define the role of C5a vs. C5b-9 in human disease has used rodents deficient in C6, yet the molecular basis for the deficiencies has not been ascertained. Oligonucleotides derived from a 493 bp EST sequence of the rat C6 gene were used to isolate full-length transcripts of rat C6 mRNA. Sequence analysis confirmed that the derived amino acid sequence for rat C6 is highly homologous to human and mouse. We identified a 31 bp deletion in exon 10 of the C6 gene that leads to C6 deficiency in a strain of PVG rats (PVG/c-) and developed a PCR-based genotyping test. In addition, we identified four point mutations in the mouse C6 gene that may result in C6 deficiency observed in the Peru-Coppock mouse strain. A serendipitous finding from this study was a coagulation defect in the C6 deficient mice and rats. C6 deficient mice or rats demonstrated prolonged tail bleeding times that was reversed by treatment with purified rat C6 protein. Further, adenosine diphosphate induced platelet aggregation were markedly reduced in C6 deficient rats. The molecular basis for these coagulations defects is unknown at present.

journal_name

Immunobiology

journal_title

Immunobiology

authors

Bhole D,Stahl GL

doi

10.1016/j.imbio.2004.08.001

subject

Has Abstract

pub_date

2004-01-01 00:00:00

pages

559-68

issue

7

eissn

0171-2985

issn

1878-3279

pii

S0171-2985(04)00071-3

journal_volume

209

pub_type

杂志文章

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