Youth Assets and Associations With Adolescent Risk Taking.

BACKGROUND: Positive youth development emphasizes that adaptive features of adolescence may contribute to teenage pregnancy prevention. METHODS: Using data from approximately 1300 seventh-ninth graders, we describe positive youth development assets (external and internal) and their association with sexual risk taking. School-, sex-, and race/ethnicity-stratified logistic or linear models assessed associations between developmental assets and 6 outcomes (continuous attitudes about teenage sex and marriage, abstinence intentions, and nonsexual risk-taking behavior; dichotomous high risk-dating behavior, friends' sexual activity, and prior sexual activity). RESULTS: Associations between developmental assets and youth sexual behavior differed by school, sex, and race/ethnicity. White female respondents showed the most consistent associations between higher amounts of each of the positive youth development assets and attitudes and behaviors conducive to delaying sexual activity while black youth showed the fewest associations. CONCLUSION: These results contribute to the positive youth development literature by identifying that relationships between assets and adolescent risk differs by race and sex.

CORRELATION OF ARTICULAR CARTILAGE THICKNESS MEASUREMENTS MADE WITH MAGNETIC RESONANCE IMAGING, MAGNETIC RESONANCE ARTHROGRAPHY, AND COMPUTED TOMOGRAPHIC ARTHROGRAPHY WITH GROSS ARTICULAR CARTILAGE THICKNESS IN THE EQUINE METACARPOPHALANGEAL JOINT.

Osteoarthritis of the metacarpophalangeal joint is common cause of lameness in equine athletes, and is hallmarked by articular cartilage damage. An accurate, noninvasive method for measuring cartilage thickness would be beneficial to screen for cartilage injury and allow for prompt initiation of interventional therapy. The objective of this methods comparison study was to compare computed tomographic arthrography (CTA), magnetic resonance imaging (MRI), and magnetic resonance arthrography (MRA) measurements of articular cartilage thickness with gross measurements in the metacarpophalangeal joint of Thoroughbred horses. Fourteen cadaveric, equine thoracic limbs were included. Limbs were excluded from the study if pathology of the metacarpophalangeal articular cartilage was observed with any imaging modality. Articular cartilage thickness was measured in nine regions of the third metacarpal bone and proximal phalanx on sagittal plane MRI sequences. After intra-articular contrast administration, the measurements were repeated on sagittal plane MRA and sagittal CTA reformations. In an effort to increase cartilage conspicuity, the volume of intra-articular contrast was increased from 14.5 ml, to maximal distention for the second set of seven limbs. Mean and standard deviation values were calculated, and linear regression analysis was used to determine correlations between gross and imaging measurements of cartilage thickness. This study failed to identify one imaging test that consistently yielded measurements correlating with gross cartilage thickness. Even with the use of intra-articular contrast, cartilage surfaces were difficult to differentiate in regions where the cartilage surfaces of the proximal phalanx and third metacarpal bone were in close contact with each other.

Placental abnormalities in equine pregnancies generated by SCNT from one donor horse.

Placental changes associated with SCNT have been described in several species, but little information is available in this area in the horse. We evaluated the ultrasonographic, gross, and histopathological characteristics of placentas from three successful and five unsuccessful equine SCNT pregnancies, established using cells from a single donor horse. Starting at approximately 6-month gestation, the pregnancies were monitored periodically using transrectal (TR) and transabdominal (TA) ultrasonography (US) to examine the placentas, fetal fluids, and fetuses. Of the five mares that aborted, one mare did so suddenly without any abnormal signs detected by US and four had enlarged umbilical vessels visible on TA-US before abortion. Placental edema (TR-US) and intravascular thrombi in the umbilical cords were seen (TA-US) in two of these four mares; one mare aborted shortly after acute placental separation was identified on TA-US. In three mares that delivered live foals, TA-US showed engorged allantoic vessels and enlarged umbilical vessels. Two of these mares had placental thickening visible on TR-US, interpreted as a sign of placentitis, that subsided after aggressive medical treatment. Seven of the eight placentas were submitted for gross and histopathological examinations after delivery. All placentas had some degree of edema, abnormally engorged allantoic vessels, and enlarged umbilical vessels. Placentitis, large allantoic vesicles, cystic pouches in the fetal part of the cord, and hemorrhages and thrombi in the umbilical vessels were detected only in placentas from mares that aborted. Equine pregnancies resulting from SCNT may be associated with placental pathologies that can be detected using ultrasonography. However, interpreting their severity is difficult. Although placental abnormalities have been observed in SCNT pregnancies in other species, to the best of our knowledge, placentitis has not been previously reported and may be an important complication of equine SCNT pregnancies, leading to pregnancy loss.

Mucopolysaccharidosis type VI in a juvenile miniature schnauzer dog with concurrent hypertriglyceridemia, necrotizing pancreatitis, and diabetic ketoacidosis.

A 7-month-old, neutered male miniature schnauzer dog with a history of cryptorchidism and umbilical hernia was referred for diabetic ketoacidosis. Clinical evaluation revealed stunted growth, skeletal abnormalities, hypertriglyceridemia, diabetic ketoacidosis, and acute necrotizing pancreatitis. Further testing was diagnostic for mucopolysaccharidosis type VI causing the stunted growth and skeletal deformities, but no connection between mucopolysaccharidosis type VI, hypertriglyceridemia, and pancreatic diseases was found.

Mucopolysaccharidose de type VI chez un jeune chien Schnauzer miniature atteint d'hypertriglycéridémie, de pancréatite nécrosante et d'acidocétose diabétique concomitantes. Un chien Schnauzer miniature castré âgé de 7 mois avec une anamnèse de cryptorchidie et d'hernie ombilicale a été référé pour une acidocétose diabétique. L'évaluation clinique a révélé une croissance arrêtée, des anomalies squelettiques, l'hypertriglycéridemie, l'acidocétose diabétique et une pancréatite nécrosante aiguë. Des tests supplémentaires ont permis de diagnostiquer une mucopolysaccharidose de type VI causant une croissance arrêtée et des difformités squelettiques, mais aucun lien avec la mucopolysaccharidose de type VI, l'hypertriglycéridémie et les maladies pancréatiques n'a été trouvé.(Traduit par Isabelle Vallières).

Syrian hamsters (Mesocricetus auratus) with simultaneous intestinal Giardia sp., Spironucleus sp., and trichomonad infections.

A commercial facility producing hamsters with a history of infection by dwarf tapeworm (Hymenolepis nana) submitted 15 animals for necropsy and postmortem parasitological and microscopic examination. No tapeworms were detected grossly or microscopically. Fecal examination including gastrointestinal mucosal smears demonstrated mixed intestinal bacteria and low numbers of Giardia sp. Histologic examination of small intestine demonstrated filling of the small intestinal crypts by large numbers of 7-9 µm × 3 µm, rod to crescent or teardrop-shaped flagellates consistent with Spironucleus sp. These organisms had two 1-µm, basophilic, oval nuclei and multiple superficial flagella-like structures. Much larger 10-15 µm × 8-10 µm, oval to pear-shaped organisms were also present in lower numbers and usually located with the crypts. These larger flagellates had multiple flagella and a basophilic rod-shaped nucleus. The larger flagellates included Giardia sp., which had an intimate interface with the surface of the mucosal epithelium, bilaterally symmetry, and binucleation. Lower numbers of trichomonads were also present and were distinguished by an undulating surface membrane and a single nucleus. The mucosa was hyperplastic and moderately inflamed. Although the tapeworm infection was resolved, diagnosis of multiple intestinal flagellates by fecal examination is complicated by the varying sensitivity and diagnostic accuracy of different types of fecal analysis for different flagellate types. Key differences in the morphology and location of the different types of flagellates as observed by histology of intestinal tissues provide important additional diagnostic information to distinguish trichomonads, Spironucleus sp., and Giardia sp.

Report of wood decay fungus Inonotus tropicalis (phylum Basidiomycota) from a dog with a granulomatous mediastinal mass.

A 75.9-kg, 3.5-year-old male Irish Wolfhound dog with a 2-3-week history of gagging and eating difficulties was referred to the University of Florida Veterinary Medical Hospital (Gainesville, Florida) for evaluation of a large cranial mediastinal mass suspected to be a thymoma or lymphosarcoma. The patient had 4 months of nearly 10 kg progressive weight loss with severe flank sensitivity and radiographically apparent lumbar vertebral changes interpreted as discospondylitis. Lab work revealed hyperglobulinemia, mild proteinuria, normal T4, negative Brucella canis titer, and negative blood and urine bacterial cultures. A thoracotomy revealed a nonresectable, destructive, space-occupying mediastinal mass resulting in euthanasia without surgical recovery. Biopsies from the mass were collected during surgery for histology. Microscopic examination revealed extensive granulomatous cellulitis and lymphadenitis characterized by central cavitated necrotic areas containing debris and degenerate neutrophils, intermediate zones of fibrovascular proliferation with marked mixed inflammation, peripheral fibrosis, frequent multinucleated macrophages, and scattered mineralization. The necrotic material contained dense mats of 2 µm wide by 8-15 µm long fungal hyphae with parallel walls, acute angle branching, frequent septae, and occasional bulb-like dilations. DNA sequencing and phylogenetic analysis of the internal transcribed spacer region confirmed the presence of a fungus in the Inonotus tropicalis group. Inonotus tropicalis is primarily a wood decay fungus that is found on dead wood from angiosperms in tropical and subtropical habitats. Isolates of the I. tropicalis group have been detected a few times from immunosuppressed human beings with X-linked granulomatous disease.

The onset of goiter in several species of sharks following the addition of ozone to a touch pool.

This report describes the onset of goiter in several species of shark following the addition of ozone to a touch pool. A detailed description of a female brown-banded bamboo shark (Chiloscyllium punctatum) that was presented with multinodular goiter is provided. Four other brown-banded bamboo sharks and 11 white-spotted bamboo sharks (Chiloscyllium plagiosum) housed in the same system developed clinical disease consistent with goiter, but two zebra bullhead sharks (Heterodontus zebra) did not. Plasma thyroxine (T4) concentration was 4.64 ng/ml before euthanasia, consistent with a diagnosis of hypothyroidism. The sharks had been chronically exposed to mean (+/- standard error) NO3-N concentrations of 35 +/- 5.12 mg/L before ozonation of the system. Ozonation of aquarium water causes a reduction in environmental iodide, which is required for thyroid hormone synthesis. Nitrate is goitrogenic and would further decrease I- absorption by competitive inhibition. Multinodular goiter is consistent with goiter caused by chronic iodide deficiency. Understanding the interaction between water chemistry and goiter development is critical to development of elasmobranch health management systems.

Gastrointestinal small-cell lymphoma with gall bladder involvement in a cat.

A 13-year-old female spayed domestic shorthair cat presented for investigation of decreased appetite and increased serum liver enzyme concentrations. An abdominal ultrasound revealed multiple sessile hyperechoic structures along the luminal aspect of the gall bladder wall and a mildly enlarged liver with hyperechoic nodules. Cholecystectomy was performed and biopsies were obtained by laparotomy. Histopathologic examination with immunohistochemistry was consistent with a diagnosis of small-cell lymphoma of T cells within the gall bladder, liver and small intestine. Clonality testing confirmed the diagnosis. The cat remains clinically stable 23 months after institution of treatment with prednisolone, chlorambucil and ursodeoxycholic acid. This is the first report of small-cell lymphoma in the gall bladder of a cat.

Allele- and tir-independent functions of intimin in diverse animal infection models.

Upon binding to intestinal epithelial cells, enterohemorrhagic Escherichia coli (EHEC), enteropathogenic E. coli (EPEC), and Citrobacter rodentium trigger formation of actin pedestals beneath bound bacteria. Pedestal formation has been associated with enhanced colonization, and requires intimin, an adhesin that binds to the bacterial effector translocated intimin receptor (Tir), which is translocated to the host cell membrane and promotes bacterial adherence and pedestal formation. Intimin has been suggested to also promote cell adhesion by binding one or more host receptors, and allelic differences in intimin have been associated with differences in tissue and host specificity. We assessed the function of EHEC, EPEC, or C. rodentium intimin, or a set of intimin derivatives with varying Tir-binding abilities in animal models of infection. We found that EPEC and EHEC intimin were functionally indistinguishable during infection of gnotobiotic piglets by EHEC, and that EPEC, EHEC, and C. rodentium intimin were functionally indistinguishable during infection of C57BL/6 mice by C. rodentium. A derivative of EHEC intimin that bound Tir but did not promote robust pedestal formation on cultured cells was unable to promote C. rodentium colonization of conventional mice, indicating that the ability to trigger actin assembly, not simply to bind Tir, is required for intimin-mediated intestinal colonization. Interestingly, streptomycin pre-treatment of mice eliminated the requirement for Tir but not intimin during colonization, and intimin derivatives that were defective in Tir-binding still promoted colonization of these mice. These results indicate that EPEC, EHEC, and C. rodentium intimin are functionally interchangeable during infection of gnotobiotic piglets or conventional C57BL/6 mice, and that whereas the ability to trigger Tir-mediated pedestal formation is essential for colonization of conventional mice, intimin provides a Tir-independent activity during colonization of streptomycin pre-treated mice.

Nitrate-induced goiter in captive whitespotted bamboo sharks Chilosryllium plagiosum.

Elasmobranch susceptibility to goiter formation in captive environments has been well documented. Until recently, most public aquariums operated under the belief that the etiology of goiter in elasmobranchs was nutritional and specifically caused by insufficient dietary iodine. Recent studies have demonstrated that high environmental nitrate (NO3-N) inhibits the ability of the thyroid gland to utilize available iodide, resulting in thyroid gland overstimulation by thyroid stimulating hormone and ultimately leading to the development of goiter. The objective of this study was to evaluate the effects of high environmental nitrate concentrations on thyroid function in juvenile whitespotted bamboo sharks Chiloscyllium plagiosum. In July 2008, five juveniles (80-150 g) were exposed to a low-nitrate environment (NO3-N concentration < 1 mg/L of water) and five were exposed to an elevated-nitrate environment (NO3-N = 70 mg/L) for 29 d in a flow-through natural seawater system. Nitrate exposure did not affect growth rates (e.g., weight, length, and condition factor) and did not alter free plasma thyroxine concentrations during the 29-d experimental period. However, histological examination of thyroid glands from sharks exposed to elevated nitrate revealed the development of diffuse hyperplastic goiter. With increasing restrictions on water use, most modern aquaria operate as recirculating systems, which results in higher and more chronic nitrate exposure for captive animals. Goiter is one of the most common health problems in captive elasmobranchs, and this study suggests that nitrate exposure is an important factor in the etiology of this disease.

Excision of a congenital laryngeal cyst in a five-month-old dog via a lateral extraluminal approach.

CASE DESCRIPTION: A 5-month-old neutered male Golden Retriever was evaluated because of moderate stridor, exercise intolerance, and dyspnea. The dog had been neutered 3 weeks previously, and the referring veterinarian identified a large fluid-filled swelling on the left lateral aspect of the larynx during anesthetic intubation for that surgery. The referring veterinarian drained fluid from the mass by use of needle centesis via the oral cavity, which resulted in temporary improvement in clinical signs; however, the clinical signs returned soon thereafter. CLINICAL FINDINGS: A large, soft, spherical mass was located between the left arytenoid and thyroid cartilages and axial to the left ceratohyoid bone, thus causing partial obstruction of the rima glottidis. Laryngoscopic examination, computed tomography (CT), and cytologic evaluation of aspirates performed before surgery; examination during surgery; and histologic evaluation of tissues following surgical excision confirmed the diagnosis of a laryngeal cyst. TREATMENT AND OUTCOME: Complete surgical excision was successfully performed via a lateral extraluminal approach to the larynx. One week after surgery, the dog coughed only occasionally. Twelve months after surgery, the owner reported that the dog was clinically normal with no recurrence of clinical signs, and laryngoscopic examination revealed no recurrence of the cyst or other pathological changes in the laryngeal region. CLINICAL RELEVANCE: Congenital laryngeal cysts are rarely reported in domestic animals. The information provided here described the CT appearance of a laryngeal cyst and the use of CT in diagnosis and surgical planning. Congenital laryngeal cysts can be resected via a lateral submucosal approach.

Iris abscesses with and without intralenticular fungal invasion in the horse.

OBJECTIVE: To describe clinical and histologic findings in horses with iris abscesses. Design Retrospective medical records study. ANIMALS STUDIED: Medical records of horses that had iris abscesses at the University of Florida Veterinary Medical Center, Peterson & Smith Equine Hospital, and Veterinary Eye Specialists of London, Ontario, from 2005 to 2008 were reviewed. PROCEDURE: Data collected from the medical records included signalment, clinical and histologic descriptions of ocular lesions, therapy, complications, and visual outcomes. RESULTS: The medical records of two Quarterhorses, one pony, one warmblood, one Westphalian, and one Arab horse with unilateral iris abscesses were identified. Mild-to-severe clinical signs of iridocyclitis were present in all six eyes with iris abscesses. The eyes of two horses with iris abscesses were also associated with deep stromal abscesses and responded to medical therapy alone in one case, and medical therapy and corneal transplantation in the other. Iris abscesses in two horses were also associated with intralenticular invasion due to a Cladosporium and a Fusarium-type fungus respectively, and resulted in enucleations. Two horses with iris abscesses and no apparent lens involvement resolved with medical therapy in one case and surgical removal of the iris abscess and medical therapy in the other. CONCLUSIONS: This is the first clinical report of iris abscesses in the horse, and the first histologic report of fungal invasion of the horse lens.

Exotic Perkinsus sp. protozoa in an imported Vietnamese ornamental clam (Tridacna crocea) maintained in a home aquarium.

An adult, hermaphroditic Tridacna crocea ornamental clam imported from Vietnam into the USA became terminally moribund with sloughed byssal tissue and incomplete extension of the poorly responsive mantle and was necropsied. Necropsy findings included emaciation, visceral mass edema, and rare multifocal, 1-mm diameter, off-white to light tan gill nodules. Histopathology revealed marked inflammation and necrosis within the visceral mass and gills, with interstitial edema and atrophy of glandular, gonadal, and muscular tissues. Inflamed tissues contained large numbers of 10-15 microm extracellular, spherical organisms with a signet-ring morphology consistent with Perkinsus spp. trophozoites. The organisms often formed clusters of two to four cells and were surrounded by a host reaction consisting of a 1-4 microm rim of amorphous eosinophilic material and two to four host hemocytes. Incubation of infected host tissues in alternative Ray's fluid thioglycollate medium (ARFTM) confirmed the presence of Perkinsus sp. hypnospores that stained blue-black with Lugol's iodine. Polymerase chain reaction assays with sequencing of products revealed a high level of nucleotide similarity, but no exact match, to known P. olseni isolates. Perkinsus sp. organisms, including P. olseni and P. marinus, which are internationally reportable, are highly pathogenic destructive protozoa capable of disrupting ecosystems populated by naïve mollusks within the USA and negatively affecting both domestic and international shellfish industries. This is the first report of an exotic Perkinsus sp. pathogen in an imported ornamental clam maintained long term in a home aquarium. However, ongoing research indicates that T. crocea from Vietnam are commonly infected by such organisms. Veterinarians, aquarium facility mangers, and veterinary clients with hobby aquariums should use appropriate caution and responsible disposal practices for clam carcasses and for water in which imported ornamental clams have been housed. Such practices will reduce the possibility of dispersing viable, exotic Perkinsus sp. organisms into domestic waters.

Transmammary infection of free-ranging Florida panther neonates by Alaria marcianae (Trematoda: Diplostomatidae).

Two freshly-dead female Florida panther (FP) neonates, Puma concolor couguar (=Puma concolor coryi), an 11-day-old and a 17-day-old, were collected in the Florida Panther National Wildlife Refuge (26 degrees 14'N, 81 degrees 36'W), Collier County, Florida. The 2 neonates were siblings and had presumably fed only on milk from the dam since birth. A 12-day-old female FP neonate was collected in the Big Cypress National Preserve (26 degrees 05'N, 81 degrees 15'W), Collier County, Florida and had also fed only on milk from the dam since birth. Milk was the only food item found in the gastrointestinal tract of these neonates. Mesocercariae and diplostomula of Alaria marcianae were collected from the lungs of the 3 neonates, indicating a transmammary route of infection. No mesocercariae, diplostomula, or mature A. marcianae were seen in the stomach or small intestine. The probable paratenic host for the A. marcianae infection in the adult Florida panther is the raccoon (Procyon lotor).

Perkinsus olseni detected in Vietnamese aquacultured reef clams Tridacna crocea imported to the USA, following a mortality event.

Morbidity and mortality were observed in a group of 30 reef clams Tridacna crocea that were imported to Florida, USA, from a Vietnamese culture facility and held in research facility aquaria. Clinical signs included an incompletely extended mantle, slow mantle responses to stimuli, and sloughing of byssal tissue beginning 2 to 5 d prior to death. Necropsy findings included emaciation, visceral mass edema, and rare multifocal 1 mm off-white to light-tan gill nodules. Histopathology revealed marked inflammation and necrosis within the visceral mass and gills, with interstitial edema and atrophy of glandular, gonadal, and muscular tissues. Inflamed tissues contained large numbers of 10 to 15 microm extracellular round organisms consistent with Perkinsus sp. trophozoites. The organisms often formed clusters of 1 to 4 cells and were surrounded by a 1 to 3 microm rim of eosinophilic material variably forming a radiating corona pattern and by 3 to 4 host hemocytes with dense round nuclei. Polymerase chain reaction assays indicated the presence of Perkinsus sp. DNA in these animals, and species-specific assays indicated the presence of P. olseni, and possibly other Perkinsus spp., but not P. marinus. Identification of Perkinsus spp. other than P. marinus in T. crocea imported from Vietnam confirms that importation of untested and unquarantined ornamental reef clams has possibly allowed incursion of P. olseni into the USA.

A neuroinductive biomaterial based on dopamine.

Chemical messengers such as neurotransmitters play an important role in cell communication, differentiation, and survival. We have designed and synthesized a bioactive biomaterial that derived its biological activity from dopamine. The resultant biodegradable polymer, PCD, has pendent groups bearing dopamine functionalities. Image analysis demonstrated that nerve growth factor-primed rat pheochromocytoma cells (PC12) and explanted rat dorsal root ganglions attached well and displayed substantial neurite outgrowth on the polymer surface. Furthermore, PCD promoted more vigorous neurite outgrowth in PC12 cells than tissue culture polystyrene, laminin, and poly(d-lysine). The histogram of neurite length of PC12 cells showed distinctive patterns on PCD that were absent on the controls. A subset of PC12 cells displayed high filopodium density on PCD. The addition of dopamine in culture medium had little effect on the differentiation of PC12 cells on tissue culture polystyrene. Tyrosine, the precursor of dopamine, did not exhibit this ability to impart specific bioactivity to an analogous polymer. Thus, the dopamine functional group is likely the origin of the inductive effect. PCD did not cause nerve degeneration or fibrous encapsulation when implanted immediately adjacent to the rat sciatic nerves. This work is a step toward creating a diverse family of bioactive materials using small chemical messengers as monomers.

B-cell depletion inhibits arthritis in a collagen-induced arthritis (CIA) model, but does not adversely affect humoral responses in a respiratory syncytial virus (RSV) vaccination model.

We report the development of a mouse B cell-depleting immunoconjugate (anti-CD22 monoclonal antibody [mAb] conjugated to calicheamicin) and its in vivo use to characterize the kinetics of CD22+ B-cell depletion and reconstitution in murine primary and secondary lymphoid tissues. The effect of B-cell depletion was further studied in a murine collagen-induced arthritis (CIA) model and a respiratory syncytial virus (RSV) vaccination model. Our results show that (1) the immunoconjugate has B-cell-specific in vitro and in vivo cytotoxicity; (2) B-cell reconstitution starts in the bone marrow and spleen around day 30 after depletion and is completed in all tissues tested by day 50; (3) B-cell depletion inhibits the development of clinical and histologic arthritis in the CIA model; (4) depletion of type II collagen antibody levels is not necessary for clinical and histologic prevention of CIA; and (5) B-cell depletion does not adversely affect memory antibody responses after challenge nor clearance of infectious virus from lungs in the RSV vaccination model. These results demonstrate for the first time that only B-cell reduction but not type II collagen antibody levels correlate with the prevention of arthritis and represent key insights into the role of CD22-targeted B-cell depletion in mouse autoimmunity and vaccination models.

Deletion of active ADAMTS5 prevents cartilage degradation in a murine model of osteoarthritis.

Human osteoarthritis is a progressive disease of the joints characterized by degradation of articular cartilage. Although disease initiation may be multifactorial, the cartilage destruction appears to be a result of uncontrolled proteolytic extracellular matrix destruction. A major component of the cartilage extracellular matrix is aggrecan, a proteoglycan that imparts compressive resistance to the tissue. Aggrecan is cleaved at a specific 'aggrecanase' site in human osteoarthritic cartilage; this cleavage can be performed by several members of ADAMTS family of metalloproteases. The relative contribution of individual ADAMTS proteases to cartilage destruction during osteoarthritis has not been resolved. Here we describe experiments with a genetically modified mouse in which the catalytic domain of ADAMTS5 (aggrecanase-2) was deleted. After surgically induced joint instability, there was significant reduction in the severity of cartilage destruction in the ADAMTS5 knockout mice compared with wild-type mice. This is the first report of a single gene deletion capable of abrogating the course of cartilage destruction in an animal model of osteoarthritis. These results demonstrate that ADAMTS5 is the primary 'aggrecanase' responsible for aggrecan degradation in a murine model of osteoarthritis, and suggest rational strategies for therapeutic intervention in osteoarthritis.