Silencing of the immunoglobulin heavy chain locus by removal of all eight constant-region genes in a 200-kb region.
Silencing or removal of individual C (constant)-region genes and/or adjacent control sequences did not generate fully deficient Ig (immunoglobulin)- mice. A reason is that different C genes share many functional tasks and most importantly are individually capable of ensuring lymphocyte differentiation. Nevertheless, incomplete arrests in B-cell development were found, most pronounced at the onset of H-chain expression. Here we show that removal of 200 kb accommodating all C genes, Cmu-Cdelta-Cgamma3-Cgamma1-Cgamma2b-Cgamma2a-Cepsilon-Calpha, stops antibody production. For this two loxP targeting constructs were introduced into the most 5' C gene and the distal alpha 3' enhancer. Cre-loxP-mediated in vivo deletion was accompanied by extensive germ-line mosaicism, which could be separated by breeding. Homozygous C-gene deletion mice did not express Ig H or L chains and flow cytometry revealed a complete block in B-cell development. However, C-gene removal did not affect DNA rearrangement processes following locus activation, as recombination efficacy appears to be similar to what is found in normal mice.
Laboratory of Developmental Immunology, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom.
Liming
L
Ren
Xiangang
X
Zou
Jennifer A
JA
Smith
Marianne
M
Brüggemann
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D003433:Crosses, Genetic; D005260:Female; D005434:Flow Cytometry; D015321:Gene Rearrangement; D020868:Gene Silencing; D018390:Gene Targeting; D007127:Immunoglobulin Constant Regions / Q000235:genetics* / Q000502:physiology; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000502:physiology; D007147:Immunoglobulin Light Chains / Q000235:genetics; D019426:Integrases / Q000378:metabolism; D019901:Locus Control Region / Q000235:genetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009030:Mosaicism; D011995:Recombination, Genetic
D007127:Immunoglobulin Constant Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; C045073:Cre recombinase; D019426:Integrases