A role for VAMP8/endobrevin in surface deployment of the water channel aquaporin 2.

Vesicle-associated-membrane protein 8 (VAMP8) is highly expressed in the kidney, but the exact physiological and molecular functions executed by this v-SNARE protein in nephrons remain elusive. Here, we show that the depletion of VAMP8 in mice resulted in hydronephrosis. Furthermore, the level of the vasopressin-responsive water channel aquaporin 2 (AQP2) was increased by three- to fivefold in VAMP8-null mice. Forskolin and [desamino-Cys(1), D-Arg(8)]-vasopressin (DDAVP)-induced AQP2 exocytosis was impaired in VAMP8-null collecting duct cells. VAMP8 was revealed to colocalize with AQP2 on intracellular vesicles and to interact with the plasma membrane t-SNARE proteins syntaxin4 and syntaxin3, suggesting that VAMP8 mediates the regulated fusion of AQP2-positive vesicles with the plasma membrane.

Mouse lymphomas caused by an intron-splicing donor site deletion of the FasL gene.

A spontaneous lymphoma was detected in mice, which was caused by a recessive autosomal mutation. The genetic basis was revealed to be a 5-bp deletion at the splicing donor site of the first intron of the FasL gene, resulting in aberrant transcripts coding for non-functional proteins. This mutation of the FasL gene caused development of lymphoma in all four mouse genetic backgrounds tested and the lymphoma was characterized by an expansion of leucocytes that were TCR+CD3+B220+CD19-CD4-CD8-. Accordingly, severe splenomegaly developed in the mutant mice. Interestingly, thymic hyperplasia was observed in mutant mice at later stages. These results underscore the functional importance of the splicing donor site in the function of the FasL gene and provide an independent evidence for a role of FasL in normal development of lymophocytes. The mutant mice offer another genetically defined mouse model for further studies of the role and mechanism of action of FasL.