Analysis of homozygous mutant chimeric mice: deletion of the immunoglobulin heavy-chain joining region blocks B-cell development and antibody production.
Using a recently described method for efficiently deriving homozygous targeted alleles in embryonic stem cells, we produced chimeric mice whose tissues were derived partially from embryonic stem cells bearing homozygous deletion of the mouse immunoglobulin heavy-chain joining (JH) region. Characterization of these chimeric mice indicated that homozygous JH deletion leads to arrest of B-cell development at an early stage, resulting in a total lack of peripheral B cells and serum IgM. These results were confirmed in mice containing the homozygous JH deletion in their germ line. This novel B-cell-deficient mouse strain provides a tool for studying the recombination and expression of exogenous immunoglobulin genes introduced into the mouse germ line.
Jakobovits
A
A
Cell Genesys Inc., Foster City, CA 94404.
Vergara
G J
GJ
Kennedy
J L
JL
Hales
J F
JF
McGuinness
R P
RP
Casentini-Borocz
D E
DE
Brenner
D G
DG
Otten
G R
GR
D000818:Animals; D000917:Antibody Formation; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D001853:Bone Marrow / Q000276:immunology; D002678:Chimera; D004247:DNA / Q000235:genetics; D004622:Embryo, Mammalian; D005434:Flow Cytometry; D015321:Gene Rearrangement; D005803:Genes, Immunoglobulin; D006579:Heterozygote; D006720:Homozygote; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007133:Immunoglobulin Joining Region / Q000235:genetics*; D007075:Immunoglobulin M / Q000235:genetics; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009000:Monocytes / Q000276:immunology; D009838:Oligodeoxyribonucleotides; D016133:Polymerase Chain Reaction / Q000379:methods; D015183:Restriction Mapping; D017384:Sequence Deletion; D013234:Stem Cells / Q000276:immunology / Q000502:physiology; D014162:Transfection
D007143:Immunoglobulin Heavy Chains; D007133:Immunoglobulin Joining Region; D007075:Immunoglobulin M; D009838:Oligodeoxyribonucleotides; D004247:DNA