We have found a new spontaneous autosomal recessive mutation in mice that causes a systemic absence of lymph nodes and Peyer's patches. The name "alymphoplasia", with the gene symbol "aly", is proposed for this mutant. The spleen of aly/aly mice is devoid of well-defined lymphoid follicles, and the thymus does not show a clear cortical-medullary distinction. The mutant homozygotes are deficient in both humoral and cell-mediated immune functions, and are highly susceptible to infections. They have a reduced level of IgM and severely depressed levels of IgG and IgA in their sera, and do not reject allogeneic skin grafts. However, they have mature T and B cells as determined from their cell surface antigens. The results of bone marrow transplantation experiments suggest a mesenchymal disorder as a possible cause of the lack of lymph nodes and of immunodeficiency in the aly mouse. The aly mutant mouse may be a useful animal model of primary immunodeficiency, as are the nu (nude) and scid (severe combined immunodeficiency) mice.

Abstract-In an attempt to elucidate whether there is a specific ␣ 1 -adrenergic receptor (␣ 1 -AR) subtype involved in the genesis or maintenance of hypertension, the ␣ 1D -AR subtype was evaluated in a model of salt-induced hypertension. The ␣ 1D -AR-deficient (␣ 1D Ϫ/Ϫ ) and control (␣ 1D ϩ/ϩ ) mice (nϭ8 to 14 in each group) were submitted to subtotal nephrectomy and given 1% saline as drinking water for 35 days. Blood pressure (BP) was monitored by tail-cuff readings and confirmed at the end point by direct intraarterial BP recording. The ␣ 1D Ϫ/Ϫ mice had a significantly (Pϭ0.0004) attenuated increase in BP response in this protocol (baseline 94.6Ϯ2.8 versus end point 107.4Ϯ4.5 mm Hg) compared with that of their wild-type counterparts (␣ 1D ϩ/ϩ ), from a baseline 97.4Ϯ2.9 to an end point 139.4Ϯ4.5 mm Hg. Seven of 15 ␣ 1D ϩ/ϩ mice died with edema, probably owing to renal failure, whereas 14 of 15 ␣ 1D Ϫ/Ϫ mice were maintained for 35 days. Body weight, renal remnant weight, and residual renal function were similar in the 2 groups, whereas the values of plasma catecholamines (epinephrine, norepinephrine, and dopamine) were higher in ␣ 1D ϩ/ϩ than in the ␣ 1D Ϫ/Ϫ mice. These data suggest that ␣ 1D -AR plays an important role in developing a high BP in response to dietary salt-loading, and that agents having selective ␣ 1D -AR antagonism could have significant therapeutic potential in the treatment of hypertension. (Hypertension. 2002;40:101-106.)

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The molecular mechanism of immunoglobulin A nephropathy (IgAN), the most common primary renal glomerular disease worldwide, is unknown. HIGA (high serum IgA) mouse is a valid model of IgAN showing almost all of the pathological features, including mesangial cell proliferation. Here we elucidate a pattern of gene expression associated with IgAN by analyzing the diseased kidneys on cDNA microarrays. In particular, we showed an enhanced expression of several genes regulating the cell cycle and proliferation, including growth factors and their receptors, as well as endothelial differentiation gene-5 (EDG5), a receptor for sphingosine 1-phosphate (SPP). One of the growth factors, platelet-derived growth factor (PDGF) induces a marked upregulation of EDG5 in proliferative mesangial cells, and promotes cell proliferation synergistically with SPP. The genomic approach allows us to identify families of genes involved in a process, and can indicate that enhanced PDGF-EDG5 signaling plays an important role in the progression of IgAN. The Pharmacogenomics Journal (2001) 1, 211-217.

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