Collapsing glomerulopathy (CG) is associated with disorders that markedly perturb the phenotype of podocytes. The kd/kd mouse has been studied for immune and genetic causes of microcystic tubulointerstitial nephritis with little attention to its glomerular lesion. Because histologic examination revealed classic morphologic features of CG, the question arises whether podocytes in kd/kd mice exhibit additional phenotypic criteria for CG. Utilizing Tg26 mice as a positive control, immunohistochemical profiling of the podocyte phenotype was conducted simultaneously on both models. Similar to Tg26 kidneys, podocytes in kd/kd kidneys showed de novo cyclin D1, Ki-67, and desmin expression with loss of synaptopodin and WT-1 expression. Electron micrographs showed collapsed capillaries, extensive foot process effacement, and dysmorphic mitochondria in podocytes. These results indicate that the kd/kd mouse is a model of CG and raise the possibility that human equivalents of the kd susceptibility gene may exist in patients with CG.J Am Soc Nephrol 16: 2847-2851. doi: 10.1681 S ince its first clinicopathologic descriptions in the 1980s, collapsing glomerulopathy (CG) is increasingly recognized as the cause of renal failure in humans and experimental animals (1-7). In addition to the unique glomerular morphology of hyperplastic and hypertrophic podocytes overlying collapsed capillary loops (1,2), a consistent feature of CG is the marked perturbation to the mature phenotype of podocytes in diseased glomeruli (8 -13). This dysregulated podocyte phenotype is captured by select immunohistochemical markers and segregates the podocyte injury in CG from other podocytopathies (8 -13). Indeed, the application of these morphologic and immunohistochemical criteria has been instrumental in characterizing several new murine models with similarities to human CG over the last two years (3-7), each in turn furthering knowledge that disruption of normal podocyte function, whether from intrinsic or extrinsic insults, is a critical step in the development of CG.The kd/kd mouse was first described over three decades ago as a distinctive model of spontaneous proliferative disease of renal epithelium in a subline of CBA/CaH mice (14). Since then, the kd/kd mouse has been studied for immune and genetic causes of its prominent microcystic tubulointerstitial nephritis with little attention to the accompanying glomerular lesion (15)(16)(17)(18)(19). Recently, the susceptibility gene for renal disease in kd/kd mice was mapped and found to encode a prenyltransferase-like mitochondrial protein (PLMP) with shared homology to human transprenyltransferase, human geranylgeranyl pyrophosphate synthase, and a putative human tumor suppressor protein (16,19). C57BL/6 (B6) mice bred homozygous for this mutant allele manifest a tubulointerstitial disease identical to the founder strain with variable onset no earlier than 8 wk of age that ultimately progresses to end-stage renal disease by 16 to 40 wk of age (18,19). Introduction of a wild-type PLMP transgene into...

Herein, we report cloning and subcellular localization of two alanine aminotransferase (ALT) isozymes, cALT and mALT, from liver of gilthead sea bream (Sparus aurata). CHO cells transfected with constructs expressing cALT or mALT as C- or N-terminal fusion with the enhanced green fluorescent protein (EGFP) showed that cALT is cytosolic, whereas mALT localized to mitochondria. Fusion of EGFP to mALT N-terminus or removal of amino acids 1-83 of mALT avoided import into mitochondria, supporting evidence that the mALT N-terminus contains a mitochondrial targeting signal. The amino acid sequence of mALT is the first reported for a mitochondrial ALT in animals.