A Forward Genetic Screen Identifies Zebrafish Mutants with Altered Susceptibility to Mm Infection
(A) Diagram of zebrafish larva anatomy showing injection sites used in this study.
(B) Schematic diagram of forward genetic screen showing derivation of F2 gynogenetic diploid embryos infected at two dpf. Potential mutants were confirmed by backcrossing the corresponding F1 female and recovering the observed mutation in the F3 generation.
(C–H) Fluorescence images of WT and mutant sibling fish at 5 dpi with equivalent bacterial inocula. Arrows, granulomas; white arrowheads, individual infected macrophages; yellow arrowheads, pairs of highly infected macrophages out of the focus plane that have not formed granulomas. Scale bars, 500 μm.
(C) WT and (D) aggregation mutant fh212 sibling.
(E) WT and (F) resistant mutant fh199 sibling.
(G) WT and (H) hypersusceptible mutant fh112 sibling.
(I and J) Fluorescence and Differential Interference Contrast (DIC) overlay of 6 dpi WT fish with granuloma (arrow) (I) and aggregation mutant fh141 sibling (J) with highly infected macrophages (arrowheads) that have not aggregated. The scale bar represents 50 μm.
This image is the copyrighted work of the attributed author or publisher, and
ZFIN has permission only to display this image to its users.
Additional permissions should be obtained from the applicable author or publisher of the image.
Reprinted from Cell, 140(5), Tobin, D.M., Vary, J.C. Jr, Ray, J.P., Walsh, G.S., Dunstan, S.J., Bang, N.D., Hagge, D.A., Khadge, S., King, M.C., Hawn, T.R., Moens, C.B., and Ramakrishnan, L., The lta4h Locus Modulates Susceptibility to Mycobacterial Infection in Zebrafish and Humans, 717-730, Copyright
(2010) with permission from Elsevier.
Full text @ Cell