PMID- 10319865
OWN - NLM
STAT- MEDLINE
DCOM- 19990525
LR  - 20211203
IS  - 1061-4036 (Print)
IS  - 1061-4036 (Linking)
VI  - 22
IP  - 1
DP  - 1999 May
TI  - Alymphoplasia is caused by a point mutation in the mouse gene encoding Nf-kappa
      b-inducing kinase.
PG  - 74-7
AB  - The alymphoplasia (aly) mutation of mouse is autosomal recessive and
      characterized by the systemic absence of lymph nodes (LN) and Peyer's patches
      (PP) and disorganized splenic and thymic structures with immunodeficiency.
      Although recent reports have shown that the interaction between lymphotoxin (LT) 
      and the LT beta-receptor (Ltbeta r, encoded by Ltbr) provides a critical signal
      for LN genesis in mice, the aly locus on chromosome 11 is distinct from those for
      LT and its receptor. We found that the aly allele carries a point mutation
      causing an amino acid substitution in the carboxy-terminal interaction domain of 
      Nf-kappa b-inducing kinase (Nik, encoded by the gene Nik). Transgenic
      complementation with wild-type Nik restored the normal structures of LN, PP,
      spleen and thymus, and the normal immune response in aly/aly mice. In addition,
      the aly mutation in a kinase domain-truncated Nik abolished its dominant-negative
      effect on Nf-kappa b activation induced by an excess of Ltbeta r. Our
      observations agree with previous reports that Ltbeta r-deficient mice showed
      defects in LN genesis and that Nik is a common mediator of Nf-kappa b activation 
      by the tumour necrosis factor (TNF) receptor family. Nik is able to interact with
      members of the TRAF family (Traf1, 2, 3, 5 and 6), suggesting it acts downstream 
      of TRAF-associating receptor signalling pathways, including Tnfr, Cd40, Cd30 and 
      Ltbeta r. The phenotypes of aly/aly mice are more severe than those of Ltbr-/-
      mice, however, indicating involvement of Nik in signal transduction mediated by
      other receptors.
FAU - Shinkura, R
AU  - Shinkura R
AD  - Department of Medical Chemistry, Kyoto University, Graduate School of Medicine,
      Japan.
FAU - Kitada, K
AU  - Kitada K
FAU - Matsuda, F
AU  - Matsuda F
FAU - Tashiro, K
AU  - Tashiro K
FAU - Ikuta, K
AU  - Ikuta K
FAU - Suzuki, M
AU  - Suzuki M
FAU - Kogishi, K
AU  - Kogishi K
FAU - Serikawa, T
AU  - Serikawa T
FAU - Honjo, T
AU  - Honjo T
LA  - eng
SI  - GENBANK/AF143094
PT  - Journal Article
PL  - United States
TA  - Nat Genet
JT  - Nature genetics
JID - 9216904
RN  - 0 (DNA, Complementary)
RN  - 0 (LTBR protein, human)
RN  - 0 (Ltbr protein, mouse)
RN  - 0 (Lymphotoxin beta Receptor)
RN  - 0 (Receptors, Tumor Necrosis Factor)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.25 (NF-kappa B kinase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - DNA, Complementary/chemistry/genetics
MH  - Humans
MH  - Lymph Nodes/enzymology/*pathology
MH  - Lymphotoxin beta Receptor
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Transgenic
MH  - Molecular Sequence Data
MH  - Peyer's Patches/enzymology/*pathology
MH  - Phenotype
MH  - Point Mutation
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - Receptors, Tumor Necrosis Factor/genetics
MH  - Sequence Alignment
MH  - Sequence Analysis, DNA
MH  - Sequence Homology, Amino Acid
MH  - Spleen/enzymology/pathology
MH  - Thymus Gland/enzymology/pathology
EDAT- 1999/05/13 02:03
MHDA- 2001/03/23 10:01
CRDT- 1999/05/13 02:03
PHST- 1999/05/13 02:03 [pubmed]
PHST- 2001/03/23 10:01 [medline]
PHST- 1999/05/13 02:03 [entrez]
AID - 10.1038/8780 [doi]
PST - ppublish
SO  - Nat Genet. 1999 May;22(1):74-7. doi: 10.1038/8780.