Professor Uniformed Services Univ. of the Hlth. Sci. Bethesda, Maryland, United States
Disclosure(s):
Charles Via: No financial relationships to disclose
Introduction/Rationale: Using the parent-into-F1 model of lupus-like nephritis, splenocytes from female BXD recombinant inbred donor mice were transferred i.v. into female B6D2F1 hybrid hosts.
Methods: The F1 splenic phenotype was evaluated at two weeks for 16 outcome variables by flow cytometry. 56 BXD strains were tested and results for each outcome variable mapped using GeneNetwork2.0.
Results: We detected a strong locus controlling variation in F1 splenocyte numbers on Chr 5 (93–103.5 Mb) with linkage as high as 5.7 (–logP). This locus contains strong candidates linked to lupus including: heparinase, Hnrnpd, and Hnrnpdl. as well as several other positional candidates: Mir703, Antxr2, Ntcctt8, Prdm8, Rasgef1b, Vamp9, Arhgap24, Mapk10, Ptpn13, Brca1a, Helq, and Antxr2. Variation in donor CD8 T cell numbers mapped to Chr 15 at ~102.3 Mb near the lupus-associated genes Itgb7 and Itga5 (–logP 4.4). Lastly, variation in donor T cell numbers mapped to several suggestive lupus-associated loci on: a) Chr 17 including the H2 locus, early complement genes (C4a,C4b,Cfb) Tnf, Lta, Ltb, and Daxx; b) Chr 9 including Il18 and Pou2af1 (BOB1); c) Chr11 includingTnip1(A20),IL3, IL4, IL5, IL13, Irf1,Th2-lcr and Anxa6; and d) Chr X including Tlr13,Il2rg, Apool and Xist
Conclusion: These results demonstrate the feasibility of this model to identify novel gene variants relevant to the development of lupus-like nephritis. Follow up studies with larger numbers of BXD strains and including male transfers will be important.
