GeneSet Information

Tier II GS135220 • aromatase activity QTL 1 (Aaiq1, Published QTL Chr 4)

DESCRIPTION:

QTL associated with aromatase activity QTL 1. This interval was obtained by using a fixed interval width of 25 Mbp around the peak marker (127792502)

LABEL:

QTL-Aaiq1-Mouse-Chr 4

SCORE TYPE:

Binary

DATE ADDED:

2012-04-02

DATE UPDATED:

2020-05-06

SPECIES:

AUTHORS:

Li N, Nakamura K, Jiang Y, Tsurui H, Matsuoka S, Abe M, Ohtsuji M, Nishimura H, Kato K, Kawai T, Atsumi T, Koike T, Shirai T, Ueno H, Hirose S

TITLE:

Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus.

JOURNAL:

Human molecular genetics Jan 2004, Vol 13, pp. 171-9

ABSTRACT:

Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE. PUBMED: 14695357
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Annotation Information



Lymphocytes (D008214)
Lupus Erythematosus, Systemic (D008180)
Aromatase (D001141)
Receptor, Insulin (D011972)
Patients (D010361)
Leukocytes (D007962)
Phosphatidylinositol 3-Kinase (D058539)
New Zealand (D009520)
Autoantigens (D001324)
Autoimmune Diseases (D001327)
Autoantibodies (D001323)
Protein-Tyrosine Kinases (D011505)
Phosphatidylinositols (D010716)
European Continental Ancestry Group (D044465)
Insulin (D007328)
Tyrosine (D014443)
Polymorphism, Genetic (D011110)
Tissues (D014024)
Up-Regulation (D015854)
Inflammation (D007249)
Phosphotransferases (D010770)
B-Lymphocytes (D001402)
abnormal inflammatory response (MP:0001845)
1-phosphatidylinositol-3-kinase activity (GO:0016303)
aromatase activity (GO:0070330)
pathogenesis (GO:0009405)

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