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.
Ren
Liming
L
Laboratory of Developmental Immunology, The Babraham Institute, Babraham, Cambridge CB2 4AT, United Kingdom.
Zou
Xiangang
X
Smith
Jennifer A
JA
Brüggemann
Marianne
M
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