Mutation of unique region of Bruton's tyrosine kinase in immunodeficient XID mice.
The cytoplasmic tyrosine kinase, Bruton's tyrosine kinase (Btk, formerly bpk or atk), is crucial for B cell development. Loss of kinase activity results in the human immunodeficiency, X-linked agammaglobulinemia, characterized by a failure to produce B cells. In the murine X-linked immunodeficiency (XID), B cells are present but respond abnormally to activating signals. The Btk gene, btk, was mapped to the xid region of the mouse X chromosome by interspecific backcross analysis. A single conserved residue within the amino terminal unique region of Btk was mutated in XID mice. This change in xid probably interferes with normal B cell signaling mediated by Btk protein interactions.
Rawlings
D J
DJ
Department of Microbiology and Molecular Genetics, University of California, Los Angeles 90024.
Saffran
D C
DC
Tsukada
S
S
Largaespada
D A
DA
Grimaldi
J C
JC
Cohen
L
L
Mohr
R N
RN
Bazan
J F
JF
Howard
M
M
Copeland
N G
NG
D000077329:Agammaglobulinaemia Tyrosine Kinase; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000201:enzymology* / Q000276:immunology; D001483:Base Sequence; D002460:Cell Line; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D005091:Exons; D005260:Female; D008040:Genetic Linkage; D007153:Immunologic Deficiency Syndromes / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008811:Mice, Inbred DBA; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D014960:X Chromosome
D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C000625951:Btk protein, mouse