Zmpste24 is an integral membrane metalloproteinase of the endoplasmic reticulum. Biochemical studies of tissues from Zmpste24-deficient mice (Zmpste24 ؊/؊ ) have indicated a role for Zmpste24 in the processing of CAAX-type prenylated proteins. Here, we report the pathologic consequences of Zmpste24 deficiency in mice. Zmpste24 ؊/؊ mice gain weight slowly, appear malnourished, and exhibit progressive hair loss. The most striking pathologic phenotype is multiple spontaneous bone fractures-akin to those occurring in mouse models of osteogenesis imperfecta. Cortical and trabecular bone volumes are significantly reduced in Zmpste24 ؊/؊ mice. Zmpste24 ؊/؊ mice also manifested muscle weakness in the lower and upper extremities, resembling mice lacking the farnesylated CAAX protein prelamin A. Prelamin A processing was defective both in fibroblasts lacking Zmpste24 and in fibroblasts lacking the CAAX carboxyl methyltransferase Icmt but was normal in fibroblasts lacking the CAAX endoprotease Rce1. Muscle weakness in Zmpste24 ؊/؊ mice can be reasonably ascribed to defective processing of prelamin A, but the brittle bone phenotype suggests a broader role for Zmpste24 in mammalian biology.metalloproteinase ͉ knockout mice ͉ brittle bones ͉ CAAX motif T he mammalian zinc metalloproteinase Zmpste24 has attracted attention because it shares a high degree of sequence identity with Ste24p, a Saccharomyces cerevisiae enzyme required for the maturation of the farnesylated mating pheromone a-factor (1-3). Ste24p plays two distinct roles in a-factor biogenesis (2, 4). First, it acts as a CAAX endoprotease, clipping off the C-terminal three amino acids from the protein (i.e., the ϪAAX of the CAAX motif) (3). Release of the ϪAAX from a-factor can also be mediated by Rce1p, the CAAX endoprotease involved in Ras processing (3). The removal of the ϪAAX exposes a carboxyl-terminal farnesylcysteine, which is methylated by Ste14p (5). Second, Ste24p clips the amino-terminal extension of a-factor, rendering it susceptible to a final endoproteolytic cleavage by Axl1p or Ste23p (6). Aside from a-factor, no other substrates for Ste24p have been identified, but other substrates likely exist because genetic screens in yeast have demonstrated that STE24 mutations can reverse the topological orientation of membrane proteins (7) and can affect the viability of yeast with mutations in genes encoding actin cytoskeleton proteins (8).Zmpste24 faithfully carries out both of Ste24p's processing steps in a-factor biogenesis and thus is a bona fide Ste24p ortholog (2, 9). Although it would be tempting to speculate that Zmpste24 processes an ''a-factor-like'' peptide in mammals, no a-factor ortholog has yet been identified. We have previously speculated that prelamin A (a precursor to lamin A, a component of the nuclear lamina) might be a Zmpste24 substrate (2, 6) because prelamin A (like yeast a-factor) is a farnesylated CAAX protein that undergoes more than one proteolytic processing step (10). After the removal of the C-terminal ϪAAX, an additional 15 res...

Luxation of the prosthesis is substantially under the control of the surgeon. It is recommended that the acetabular cup be inserted at an angle of lateral opening of 35 degrees to 45 degrees. In those cases of THR luxation in which an inappropriate angle of lateral opening is identified, acetabular revision arthroplasty generally results in a good clinical outcome.

Strains of Cryptococcus spp appeared to have host specificity in dogs and cats. Differences in lesion distribution between geographic locations may reflect strain differences or referral bias. Antigen assays alone may not be sufficient for diagnosis of cryptococcosis in cats and dogs.

Although histologic examination following stereotactic or surgical brain biopsy is required for definitive antemortem diagnosis of intracranial neoplasms, these tumors are often associated with magnetic resonance (MR) imaging features that warrant a presumptive or prioritized differential diagnosis. The MR imaging features of common canine central nervous system (CNS), adenohypophyseal, and metastatic intracranial neoplasms are reviewed. Characterization of neoplasms by histologic type and biological grade is based on the 2007 World Health Organization classification system for CNS tumors in humans.