Xanthinuria in a familial group of Munchkin cats and an unrelated domestic shorthair cat.

CASE SERIES SUMMARY: Four confirmed cases of xanthinuria in cats, and one suspected case based on pedigree analysis, were identified. Clinical presentations varied and included haematuria, pollakiuria, dysuria, and urethral and ureteral obstruction. All cats had upper urinary tract uroliths. Diagnosis was obtained through infrared mass spectrometry of uroliths or urine. Clinical signs commenced at 3-8 months of age and reduced in all cats in the medium to long term after the introduction of a protein-restricted diet. Four cats were castrated males and one was a spayed female. Cases consisted of four Munchkin pedigree cats and one unrelated domestic shorthair cat. All four affected Munchkin pedigree cats were related, with three cases full siblings and the fourth case a half-sibling. No connection to the Munchkin pedigree could be established for the domestic shorthair cat. A candidate causative genetic variant (XDH p.A681V) proposed for this cat was excluded in the Munchkin family. RELEVANCE AND NOVEL INFORMATION: All affected cats presented diagnostic challenges and routine urinalysis was insufficient to obtain a diagnosis. Cases of feline xanthinuria may be underdiagnosed due to situations where uroliths cannot be retrieved for analysis and there is an inability to make a diagnosis using crystal morphology alone on routine urinalysis. Metabolic screening of urine may provide an effective mechanism to confirm xanthinuria in suspected cases where uroliths are inaccessible or absent. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs and urethral obstruction developing secondary to xanthine urolithiasis. A protein-restricted diet appears to reduce clinical signs as part of long-term management. PLAIN LANGUAGE SUMMARY: Four closely related Munchkin cats and one domestic shorthair cat were found with a suspected genetic disease causing high levels of xanthine in their urine. The case series looks at similarities and differences in their clinical signs, as well as difficulties experienced in obtaining a correct diagnosis. All cats had upper urinary tract stones and required metabolic testing of the stones or urine to diagnose. All cats were young when their clinical signs started and were on a high-protein diet. Four cats were desexed males and one was a desexed female. A genetic variant that may have caused the disease in the domestic shorthair cat was ruled out in the Munchkin family. Cases of high xanthine levels in feline urine may be underdiagnosed as the stones may not be accessed for testing. In this case series, male cats were more common. Their anatomy may increase the risk of lower urinary tract signs. A protein-restricted diet appears to reduce clinical signs as part of long-term management.

Brain magnetic resonance imaging and computed tomography findings in cats and dogs with central nervous system cryptococcosis in Australia: 23 cases (2009-2020).

OBJECTIVE: To describe the imaging findings in Australian cats and dogs with CNS cryptococcosis. ANIMALS: 23 cases (10 cats; 13 dogs) with CNS cryptococcosis and brain MRI or CT studies available to review. METHODS: Retrospective, multi-institutional case series. Brain MRI or CT studies were reviewed by a board-certified radiologist. Imaging findings were described and the differences between cats and dogs explored. RESULTS: Morphologic features were consistent with extra-axial lesions in all (n = 13) dogs and either intra-axial (5/10) or extra-axial (4/10) lesions in cats, with 1 cat having no detectable lesions in low-field brain MRI scans. Meningeal abnormalities were most common, followed by forebrain and cerebellar lesions. Intracranial MRI lesions were typically T2 hyperintense and T1 hypo- to isointense. Four cases had T2 hypointense lesions affecting the brain, sinonasal cavity, or regional lymph nodes. Intracranial CT lesions were mostly soft tissue attenuating. Contrast enhancement was present in all cases with contrast series available, with ring enhancement shown only in cats. Osteolysis was more common in dogs than cats, particularly affecting the cribriform plate. All 13 dogs and many (6/10) cats had at least 1 lesion affecting sinonasal or contiguous tissues, and locoregional lymphadenomegaly was common (7/10 cats; 11/13 dogs). CLINICAL RELEVANCE: Imaging lesions in cryptococcal meningoencephalitis were extra-axial in dogs but could be intra-axial or extra-axial in cats. Careful examination for extracranial lesions (sinonasal, retrobulbar, facial soft tissue, tympanic bullae, or locoregional lymph nodes) is important to provide alternative safe biopsy sites. T2 hypointense lesions, while rare, should prompt consideration of cryptococcosis.

Pentalogy of Cantrell in Two Neonate Littermate Puppies: A Spontaneous Animal Model Suggesting Familial Inheritance.

Developmental anomalies are an important cause of stillbirth and early perinatal death in companion animals. Many of these disorders remain poorly understood and provide an opportunity as a spontaneous animal model for human disease. Pentalogy of Cantrell is a rare congenital syndrome described in human neonates. It is a ventral midline closure defect with a proposed familial inheritance in humans. This syndrome involves five defects, including the thoracoabdominal wall, sternal, diaphragmatic, pericardial and cardiac malformations. Diverse expressions of these defects have been described in humans and sporadically in domestic animals. This severe syndrome commonly harbors a poor prognosis, posing an ethical and surgical dilemma. To better understand this syndrome and its presentation in dogs, we describe two rare cases of Pentalogy of Cantrell in a litter of papillon dogs. The affected puppies had anomalies compatible with the Pentalogy of Cantrell, including thoracoabdominal schisis, ectopia cordis, sternal cleft, pericardial agenesis, and diaphragmatic defects. The diagnosis was confirmed by advanced imaging (computed tomography) and postmortem examinations. The family history of this litter was explored and other cases in domestic animals were reviewed. This is the first report of the complete Pentalogy of Cantrell with ectopia cordis in the dog and the only report on papillons. Similar to human cases, possible familial inheritance and suspected male gender bias were observed. Further research on this novel animal model, its pathogenesis and its hereditary basis, may be helpful in better understanding this rare developmental disorder.

Investigation of scan delays for CT evaluation of inner wall layering and peak enhancement of the canine stomach and small intestine using a 20 second fixed-injection-duration and bolus tracking technique.

Many gastrointestinal diseases affect the mucosal layer, suggesting that on computed tomography (CT) examination, detection of consistent inner wall layering of the gastrointestinal tract may aid in detection of disease. Changes in wall enhancement can also characterise specific diseases and provide prognostic information. The objectives of this mixed retrospective and prospective analytical study were therefore to identify the scan delays for peak detection of canine stomach and small intestinal inner wall layering and enhancement when using a 20 s fixed-injection-duration and bolus tracking technique. For each patient, 700 mg I/kg iohexol was administered intravenously. Bolus tracking was used to determine aortic arrival. Diagnostic scans were performed after a post-aortic arrival scan delay. Postcontrast CT series were grouped according to post-aortic arrival scan delay: 5 s (n = 17), 10 s (n = 18), 15 s (n = 23), 20 s (n = 10), 25 s (n = 6), 30 s (n = 14), 35 s (n = 17), 40 s (n = 24), and 180 s (n = 60). The stomach and small intestine were assessed for the presence of a contrast-enhancing inner wall layer and wall enhancement. Statistical modeling showed that the scan delays for peak inner wall layering and enhancement were 10 and 15 s for the small intestine, respectively, and 40 s for the stomach. For the injection protocol used in this study, assessment of the canine gastrointestinal tract may use scan delays of 10-15 s and 40 s.

Zinc toxicosis in a cat associated with ingestion of a metal screw nut.

Case summary: A 3-year-old female neutered domestic shorthair cat was presented for vomiting, inappetence and weight loss. The cat developed moderately regenerative anaemia, moderately increased alanine transaminase and alkaline phosphatase activities, hyperbilirubinaemia and prolonged activated partial thromboplastin time. Abdominal ultrasound identified gastric wall thickening and changes suggestive of pancreatitis. Gastroduodenoscopy identified a metal screw nut in the pylorus, which was removed with rat tooth forceps. Metal analysis and serum zinc concentration using leftover serum collected at admission were performed after screw nut removal. Serum zinc concentration was markedly elevated, confirming a diagnosis of zinc toxicosis. Metal analysis of the screw nut showed that the major metal component was zinc. The cat recovered after screw nut removal and supportive care. Clinical signs resolved and the serum zinc concentration reduced significantly after screw nut removal. Relevance and novel information: Reports of zinc toxicosis in cats are scarce, possibly due to the more discriminating eating habits of this species. To our knowledge, this is the first report of zinc toxicosis causing haemolytic anaemia, liver enzyme activity increases, gastrointestinal signs and pancreatitis in a cat associated with ingestion of a zinc-containing metal object.

The effect of CT and MRI with and without arthrography on the appearance of the feline carpal ligaments.

BACKGROUND: The current diagnosis of feline carpal injuries is based on radiographic examination including stress views and computed tomography; however, these techniques do not allow for direct evaluation of the carpal ligaments. The purpose of this cadaveric study was to assess the ability of CT arthrography (CTA) and MR arthrography (MRA) to provide this information using a single contrast mixture. A protocol for intra-articular injection of the feline carpus was also described. A contrast solution containing gadolinium and iohexol with a 50% gadolinium solution (Magnevist-gadolinium 0.5 mmol/mL diluted to a 0.05 mmol/mL solution) and 50% of iodine (Iohexol-iodine 300mgI/mL) was injected into the antebrachiocarpal and middle carpal joints of feline carpi using fluoroscopic guidance. RESULTS: CTA allowed for identification of intra-articular ligaments and the silhouette of select extra-articular ligaments when there was adequate joint distension, however it was not considered to be superior to MRI. MRA allowed for improved identification of the dorsal radiocarpal, accessorioulnocarpal, accessorioquartile, short ulnar and short radial collateral ligaments. CONCLUSION: In this ex-vivo study, combined CTA and MRA enhanced the appearance of the feline carpal ligaments and may provide a foundation for future studies in the diagnosis of carpal injuries.

Computed Tomographic Evaluation of the Accuracy of Minimally Invasive Sacroiliac Screw Fixation in Cats.

OBJECTIVES: The aim of this study was to report the use of computed tomography (CT) for postoperative evaluation of the accuracy of sacroiliac reduction and minimally invasive screw fixation in a series of five cats. METHODS: Medical records between January 2016 and March 2017 of cats presenting to the author's institution were reviewed. Included were cats that had undergone minimally invasive sacroiliac screw fixation with a complete medical record and pre- and postoperative radiographs. Screw size was obtained from the medical records. CT images were acquired prospectively and evaluated to assess joint reduction, relative screw size and screw positioning. RESULTS: Six sacroiliac luxations and 6 screws were available. Fixation was achieved with either a 2.4 (n = 1) or 2.7 mm (n = 5), 316L stainless steel, cortical bone screw. Mean screw size as a proportion of sacral diameter was 47.7%. Sacroiliac reduction >90% in the craniocaudal plane and sacral screw purchase >60% of the sacral width were achieved in 3/5 cases. Mean dorsoventral screw angulation was 1.6 degrees (range: -9.7 to 11.7 degrees) and craniocaudal angulation was -4.5 degrees (range: -16.6 to 6.6 degrees). Complications included screw loosening in the one case of bilateral repair and penetration of the neural canal in one case which was not detected with postoperative radiographic evaluation. CLINICAL SIGNIFICANCE: CT evaluation provides a useful method for the assessment of sacroiliac reduction and the accuracy of screw placement.

Magnetic resonance imaging in dogs with neuroangiostrongyliasis (rat lungworm disease).

The magnetic resonance imaging (MRI) appearance of the brain and spinal cord in humans with neuroangiostrongyliasis (NA) due to Angiostrongylus cantonensis infection has been well reported. Equivalent studies in animals are lacking. This case series describes clinical and MRI findings in 11 dogs with presumptively or definitively diagnosed NA. MRI of the brain and/or spinal cord was performed using high-field (1.5 T) or low-field (0.25 T) scanners using various combinations of transverse, sagittal, dorsal and three-dimensional (3D) T1-weighted (T1W), transverse, sagittal and dorsal T2-weighted (T2W), T2W fluid-attenuated inversion recovery (FLAIR) and T2*-weighted (T2*W) gradient echo (GRE), dorsal T2W short tau inversion recovery (STIR) and post-gadolinium transverse, sagittal, dorsal and 3D T1W and transverse T2W FLAIR sequences. In 4/6 cases where the brain was imaged, changes consistent with diffuse meningoencephalitis were observed. Evidence of meningeal involvement was evident even when not clinically apparent. The spinal cord was imaged in 9 dogs, with evidence of meningitis and myelitis detected in regions consistent with the observed neuroanatomical localization. Pathognomonic changes of neural larva migrans, as described in some human patients with NA, were not detected. NA should be considered in the differential diagnosis of dogs with MRI evidence of focal or diffuse meningitis, myelitis and/or encephalitis, especially in areas where A. cantonensis is endemic. If not precluded by imaging findings suggestive of brain herniation, cerebrospinal fluid (CSF) collection for cytology, fluid analysis, real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) testing should be considered mandatory in such cases after the MRI studies.

Ventilated postmortem computed tomography to evaluate the lungs of dogs with and without focal lung lesions.

OBJECTIVE: To identify the optimal ventilation pressure for ventilated postmortem CT assessment of the lungs in cadaveric dogs and compare the optimal ventilation pressures between dogs with and without focal lung lesions. SAMPLE: 12 cadaveric dogs. PROCEDURES: CT was performed with dogs positioned in sternal recumbency within 30 to 180 minutes after death. After orotracheal intubation, lungs were aerated to ventilation pressures of 0, 10, 15, 20, 25, 30, and 35 cm H2O. Lung attenuation measurements were made at 5 predetermined anatomical locations with use of a multi-image analysis graphic user interface tool. Lungs were considered hyperaerated (-1000 to -901 HU), normo-aerated (-900 to -501 HU), poorly aerated (-500 to -101 HU), and nonaerated (-100 to 100 HU) on the basis of lung attenuation values. Optimal ventilation pressure was defined as the pressure at which the percentage of normo-aerated lung was greatest. For analysis, dogs were assigned to one group when focal lung lesions were evident and to another group when lesions were not evident. RESULTS: Median optimal ventilation pressure was significantly higher for those dogs with lung lesions (35 cm H2O), compared with those without (25 cm H2O). CONCLUSIONS AND CLINICAL RELEVANCE: A ventilation pressure of 35 cm H2O may be considered for ventilated postmortem CT to determine the presence of focal lung lesions; however, further investigation is required.

Hepatic computed tomography and cholangiography by use of gadoxetic acid in healthy cats.

OBJECTIVE: To evaluate 3 doses of gadoxetic acid (Gd-EOB-DPTA) for hepatic CT and cholangiography in cats and to determine optimal timing for hepatobiliary image acquisition and evaluation of the contrast-enhanced hepatobiliary anatomy. ANIMALS: 6 healthy cats. PROCEDURES: Cats were anesthetized; sequential CT scans were performed 0, 5, 25, 45, 65, and 85 minutes after IV administration of Gd-EOB-DTPA at low (0.0125 mmol/kg), medium (0.1 mmol/kg), and high (0.3 mmol/kg) doses. Hepatobiliary enhancement for each dose was objectively assessed over time and by use of a subjective semiquantitative visual assessment score. RESULTS: No contrast-related adverse effects were detected. Each increase in dose of contrast medium resulted in a significant increase in HU across the hepatobiliary system. The liver had a significantly higher number of HU at 45 minutes, with homogenous enhancement at all doses of contrast medium. Contrast-enhanced cystic and bile duct HU were significantly higher and maximal at 65 minutes. Contrast-enhanced gallbladder HU did not plateau by 85 minutes. At a high dose of contrast medium, 12 of 60 (20%) biliary tract scores indicated no enhancement, 34 (57%) indicated poor enhancement, and 14 (23%) indicated moderate enhancement. No cat had excellent enhancement of the biliary tract at any dose. CONCLUSIONS AND CLINICAL RELEVANCE: Gd-EOB-DTPA-enhanced hepatic CT and cholangiography in cats were safely performed and provided good hepatic enhancement but poor to moderate enhancement of the biliary tract. This technique may be useful for assessing the liver parenchyma in cats, but its value for assessing the biliary tract is questionable.

High field magnetic resonance imaging anatomy of feline carpal ligaments is comparable to plastinated specimen anatomy.

Feline carpal ligament injuries are often diagnosed indirectly using palpation and stress radiography to detect whether there is instability and widening of joint spaces. There are currently no reports describing normal feline carpal ligament anatomy and the magnetic resonance imaging (MRI) appearance of the carpal ligaments. The objective of this prospective, anatomic study was to describe normal feline carpal ligament anatomy using gross plastinated specimens and MRI. We hypothesized that MRI could be used to identify the carpal ligaments as previously described in the dog, and to identify species specific variations in the cat. The study was conducted using feline cadaver antebrachii that were radiographed prior to study inclusion. Three limbs were selected for MRI to confirm repeatability of anatomy between cats. The proton density weighted pulse sequence was used and images were acquired in transverse, dorsal, and sagittal planes. Following MRI, the limbs were plastinated and a collagen stain was used to aid in identification of carpal ligament anatomy. These limbs were sliced in sagittal section, and a further six paired limbs were included in the study and sliced in transverse and dorsal planes. Anatomic structures were initially described using MRI and then subjectively compared with gross plastinated specimens. Readers considered the transverse MRI plane to be most useful for visualizing the majority of the carpal ligaments. Findings indicated that MRI anatomy of the carpal ligaments was comparable to plastinated anatomy; therefore MRI appears to be a beneficial imaging modality for exploration of feline carpal pathology.

Use of gadoxetic acid for computed tomographic cholangiography in healthy dogs.

OBJECTIVE To evaluate the effect of gadoxetic acid (contrast) dose on biliary tract enhancement, determine the optimal time after contrast injection for CT image acquisition, and assess the feasibility of CT cholangiography in sedated dogs. ANIMALS 8 healthy dogs. PROCEDURES The study had 2 parts. In part 1, 4 dogs were anesthetized and underwent CT cholangiography twice. Gadoxetic acid was administered IV at a low dose (0.025 mmol/kg) for the first procedure and high dose (0.3 mmol/kg) for the second procedure. Serial CT scans were obtained at predetermined times after contrast injection. In part 2, 4 dogs were sedated and underwent CT angiography 85 minutes after IV administration of the high contrast dose. Contrast enhancement of the biliary tract on all scans was objectively assessed by measurement of CT attenuation and qualitatively assessed by use of a subjective 4-point scoring system by 3 independent reviewers. All measurements were compared over time and between contrast doses for the dogs of part 1. Subjective measurements were compared between the sedated dogs of part 2 and anesthetized dogs of part 1. RESULTS Enhancement of the biliary tract was positively associated with contrast dose and time after contrast injection. Optimal enhancement was achieved 65 minutes after contrast injection. Subjective visualization of most biliary structures did not differ significantly between sedated and anesthetized dogs. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated CT cholangiography with gadoxetic acid was feasible in sedated dogs. The high contrast dose provided better visualization of biliary structures than the low dose; CT scans should be obtained 65 minutes after contrast injection.

Caecocolic intussusception associated with a caecal polyp and concurrent hepatocellular carcinoma in a cat.

CASE SUMMARY: A 17-year-old female neutered domestic shorthair cat presented for several days of reduced faecal volume and a rectal prolapse. Physical examination revealed a 2 cm rectal prolapse, hepatomegaly and a low body condition score of 3/9. Haematology and biochemistry revealed a mild non-regenerative anaemia (haematocrit 24.5%; reference interval [RI] 30.3-52.3%), a mild mature neutrophilia (16.21 × 109/l; RI 1.48-10.29 × 109/l) and a mild increase in alanine aminotransferase activity (222 IU/l; RI 12-130 IU/l). Abdominal radiographs identified hepatomegaly. The rectal prolapse was reduced under general anaesthesia. Abdominal ultrasound identified a caecocolic intussusception and a large hepatic mass. Thoracic radiographs were unremarkable. Hepatic fine-needle aspirate cytology revealed well-differentiated hepatocytes. A typhlectomy was performed and the quadrate liver lobe, with mass, was resected. Gross examination of the caecum identified a focal polyp; histopathology showed moderate plasmacytic-lymphocytic typhlitis and reactive mucosal-associated lymphoid tissue. The hepatic mass was diagnosed as a well-differentiated hepatocellular carcinoma. Six weeks postoperatively the cat had gained 0.5 kg, had an improved body condition score of 5/9 and resolution of clinical signs. The cat died acutely 1 year later from an unknown cause. RELEVANCE AND NOVEL INFORMATION: Caecocolic intussusception is rare in cats and uncommon in dogs. This is the third report in a cat and the first associated with a caecal polyp. As reported in dogs, the outcome following surgery was good. Hepatocellular carcinoma is a rarely reported feline neoplasm, which may have a good prognosis with surgical resection.

EFFECTS OF TWO CONTRAST INJECTION PROTOCOLS ON FELINE AORTIC AND HEPATIC ENHANCEMENT USING DYNAMIC COMPUTED TOMOGRAPHY.

This prospective study compared aortic and hepatic enhancement achieved using a contrast injection protocol with a fixed rate of 5 ml/s vs. that achieved using a protocol with fixed injection duration of 20 s in eight cats. Cats were assigned into two groups (Group 1, rate 5 ml/s; Group 2, duration 20 s). The dose of contrast was the same in both groups (740 mgI/kg). Regions of interest (ROI) were drawn in the aorta and liver for transverse scans acquired at the hepatic hilus. Time to peak aortic enhancement occurred significantly earlier in Group 1 (M = 11s, SD = 1.63) than in Group 2 (M = 25.5 s, SD = 2.51). Peak aortic enhancement was significantly higher in Group 1 (M = 1906.51 HU, SD = 368.64) than in Group 2 (M = 745.08 HU, SD = 201.84). Duration of aortic enhancement equal to or above 300 HU was statistically longer in Group 2 (M = 24.5 s, SD = 8.39) than in Group 1 (M = 10 s, SD = 1.63). There were no significant differences in time to peak liver enhancement, peak liver enhancement, or duration of hepatic arterial phase between groups. Findings supported the hypothesis that longer injection duration results in a broader bolus geometry with a longer time to peak and a lower peak aortic enhancement in cat. This strong influence of injection duration on timing of aortic enhancement may help future users optimize protocols for CT angiography of the aorta and multiphasic evaluation of the liver, pancreas, and small intestine.

Effects of stifle flexion angle and scan plane on visibility of the normal canine cranial cruciate ligament using low-field magnetic resonance imaging.

Low-field magnetic resonance imaging (MRI) is commonly used to evaluate dogs with suspected cranial cruciate ligament injury; however, effects of stifle positioning and scan plane on visualization of the ligament are incompletely understood. Six stifle joints (one pilot, five test) were collected from dogs that were scheduled for euthanasia due to reasons unrelated to the stifle joint. Each stifle joint was scanned in three angles of flexion (90°, 135°, 145°) and eight scan planes (three dorsal, three axial, two sagittal), using the same low-field MRI scanner and T2-weighted fast spin echo scan protocol. Two experienced observers who were unaware of scan technique independently scored visualization of the cranial cruciate ligament in each scan using a scale of 0-3. Visualization score rank sums were higher when the stifle was flexed at 90° compared to 145°, regardless of the scan plane. Visualization scores for the cranial cruciate ligament in the dorsal (H (2) = 19.620, P = 0.000), axial (H (2) = 14.633, P = 0.001), and sagittal (H (2) = 8.143, P = 0.017) planes were significantly affected by the angle of stifle flexion. Post hoc analysis showed that the ligament was best visualized at 90° compared to 145° in the dorsal (Z = -3.906, P = 0.000), axial (Z = -3.398, P = 0.001), and sagittal (Z = -2.530, P = 0.011) planes. Findings supported the use of a 90° flexed stifle position for maximizing visualization of the cranial cruciate ligament using low-field MRI in dogs.

Mechanical destabilization induced by controlled annular incision of the intervertebral disc dysregulates metalloproteinase expression and induces disc degeneration.

STUDY DESIGN: An investigation of mechanical destabilization of the lumbar ovine intervertebral disc (IVD) inducing IVD degeneration (IVDD) as determined by multiparameter outcome measures (magnetic resonance imaging [MRI], IVD composition, biomechanical testing, gene profiling, immunohistochemistry, and immunoblotting). OBJECTIVE: To assess the effect of IVD mechanical destabilization on matrix protein and metalloproteinase gene expression to investigate the pathophysiological mechanisms of lumbar IVDD. SUMMARY OF BACKGROUND DATA: Several earlier studies have used annular transection to induce IVDD in sheep, but none have optimized or validated the most appropriate lesion size. METHODS: The annulus fibrosus (AF) incision inducing maximal change in IVD biomechanics was applied to L1-L2, L3-L4, and L5-L6 discs in vivo to compare with a sham procedure at 3 months post operation. IVDs were evaluated by MRI, biomechanics, histopathology, proteoglycan and collagen content, gene expression, and aggrecan proteolysis by Western blotting. RESULTS: Significant changes were observed in lesion (6 × 20 mm(2)) compared with sham IVDs at 3 months post operation: reduced disc height on MRI; increased neutral zone in biomechanical testing; depleted proteoglycan and collagen content in the nucleus pulposus (NP) and lesion half of the AF but not in the contralateral AF; increased messenger RNA for collagen I and II, aggrecan, versican, perlecan, matrix metalloproteinase (MMP)-1 & 13, and ADAMTS-5, in the lesion-site AF and NP but not in the contralateral AF. ADAMTS-4 messenger RNA was increased in the lesion-site AF but decreased in the NP. Despite an upregulation in MMPs, there was no change in MMP- or ADAMTS-generated aggrecan neoepitopes in any region of the IVD in lesion or sham discs. CONCLUSION: Lumbar IVDD was reproducibly induced with a 6 × 20 mm(2) annular lesion, with focal dysregulation of MMP gene expression, cell cloning in the inner AF, loss of NP aggrecan, and disc height. Loss of aggrecan from the NP was not attributable to increased proteolysis in the interglobular domain by MMPs or ADAMTS.