WIP null mice display a progressive immunological disorder that resembles Wiskott-Aldrich syndrome.
The Wiskott-Aldrich syndrome (WAS) is an X-linked immunodeficiency syndrome caused by mutations in the WAS protein (WASP). This participates in signalling and cytoskeletal homoeostasis, and some of its activities are regulated by its binding to the WASP interacting protein (WIP). WIP deficiency, however, has not yet been shown to be of pathological significance in humans. Here we show that, in WIP null (WIP(-/-)) mice, it produces haematological alterations and anatomical abnormalities in several organs, most probably as a consequence of autoimmune attacks. Granulocytosis and severe lymphopenia are associated with a proportional increase in segmented cells and fewer bone marrow erythrocytes and lymphocytes. Splenomegaly is accompanied by an increase of haematopoietic tissue and red pulp, reduction of the white pulp, and fewer B (B220(+)) lymphocytes (also apparent in the lymph nodes and Peyer's patches). Ulcerative colitis, interstitial pneumonitis, glomerular nephropathy with IgA deposits, autoantibodies, and joint inflammation are also evident. These progressive immunological disorders closely mimic those seen in WAS. WIP deficiency may thus be implicated in some cases in which mutations in the gene encoding WASP are not detected.
Curcio
C
C
Department of Clinical and Biological Sciences, University of Torino, Italy.
Pannellini
T
T
Lanzardo
S
S
Forni
G
G
Musiani
P
P
Antón
I M
IM
D000818:Animals; D001168:Arthritis / Q000235:genetics; D001323:Autoantibodies / Q000097:blood; D001402:B-Lymphocytes / Q000276:immunology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000235:genetics / Q000473:pathology; D003598:Cytoskeletal Proteins; D004906:Erythrocyte Count; D005260:Female; D005434:Flow Cytometry; D005921:Glomerulonephritis / Q000235:genetics / Q000473:pathology; D007422:Intestines / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008168:Lung / Q000473:pathology; D017563:Lung Diseases, Interstitial / Q000235:genetics / Q000473:pathology; D008198:Lymph Nodes / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D023421:Models, Animal; D010976:Platelet Count; D013154:Spleen / Q000276:immunology; D014923:Wiskott-Aldrich Syndrome / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D051316:Wiskott-Aldrich Syndrome Protein / Q000378:metabolism
D001323:Autoantibodies; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C491671:Waspip protein, mouse; D051316:Wiskott-Aldrich Syndrome Protein