Mucosal Hyperplasia Research Articles

TL1A and DR3, a TNF family ligand‐receptor pair that promotes lymphocyte costimulation, mucosal hyperplasia, and autoimmune inflammation

DR3 (TNFRSF25) is a member of the tumor necrosis factor receptor (TNFR) superfamily expressed primarily on lymphocytes and is a receptor for the TNF family cytokine TL1A (TNFSF15). DR3 costimulates T-cell activation, but it is unique among these receptors in that it signals through an intracytoplasmic death domain and the adapter protein TRADD (TNFR-associated death domain). TL1A costimulates T cells to produce a wide variety of cytokines and can promote expansion of activated and regulatory T cells in vivo. Studies in mice deficient in DR3 or TL1A or in animals treated with antibodies that block the activity of TL1A have revealed a specific role for DR3 in enhancing effector T-cell proliferation at the site of tissue inflammation in autoimmune disease models. DR3 appears to be required in autoimmune disease models dependent on a variety of different T-cell subsets and also invariant natural killer T (iNKT) cells. Chronic expression of TL1A induces a distinct interleukin-13-dependent pathology in the small intestine marked by goblet cell hyperplasia and other features associated with allergic and anti-parasitic responses. These studies suggest that TL1A may be a viable target for therapies designed to inhibit the T-cell-dependent component of diverse autoimmune diseases.

Correlation of cone beam computed tomography (CBCT) findings in the maxillary sinus with dental diagnoses: a retrospective cross-sectional study

This study was conducted to assess the coincidence of mucosal hyperplasia in the maxillary sinus and related clinical diagnoses of posterior maxillary teeth found in cone beam computed tomography (CBCT) scans. A total of 204 patients who underwent CBCT examinations between 2006 and 2008 were evaluated retrospectively. Clinical and CBCT findings were correlated using patient records. Absolute frequencies, odds ratios (OR), and 95% confidence intervals (95% CI) were calculated for statistical evaluations. There was a pronounced association between periodontitis and radiological signs of sinusitis. Basal mucosal wall thickening was more likely in patients with decayed and non-vital teeth compared to patients with sound teeth (OR = 5.2; 95% CI = 1.2-23.1). Basal mucosal wall thickening was also more likely than total mucosal thickening (OR = 10.4; 95% CI = 2.6-42.2). Patients with decayed and endodontically treated teeth were more likely to exhibit involvement of the basal wall (OR = 9.2; 95% CI = 3.3-25.2) than were patients with healthy teeth. CBCT examinations revealed a correlation between basal mucosal thickening in the maxillary sinus and decayed posterior maxillary teeth or periodontitis. Chronic symptoms involving the sinuses are one of the most common reasons for patients to consult physicians. One reason for chronic orofacial pain is the prevalence of undiagnosed sinus conditions.

The risk factor of gallbladder cancer: Hyperplasia of mucous epithelium caused by gallstones associates with p16/CyclinD1/CDK4 pathway

Backgrounds The mucosa of gallbladder stimulated with gallstones and accompanied with abnormalities in bile composition, is the origin of biliary disease, which could induce metaplasia, simple hyperplasia, atypical hyperplasia and even carcinoma in situ and invasive carcinoma in gallbladder mucosa. Methods To determine the disorder of the balance between cell proliferation and cell cycle or apoptosis in gallbladder cancer accompanied with gallstones, removal of the gallbladder due to gallstones specimens of 88 cases were collected randomly, including a variety of 54 cases for hyperplasia, 27 cases for gallbladder cancer and 7 cases for normal gallbladder. The expressions of key cell cycle factors were detected by in situ hybridization, immunohistochemistry and Western blot. Results The expressions of CDK4 and Cyclin D1 increased along with progression of gallbladder mucosa hyperplasia; and showed highest expression in cancer group. On the contrary, p16 decreased to the lowest level in gallbladder cancer. The increased apoptotic index analyzed by TUNEL assay rose along with malignant degree to the highest level in undifferentiated carcinoma. Conclusions Our results suggest that changes of these signals have effect on breaking the balance of proliferation and death of gallbladder epithelial cells, even on inducing gallbladder cancer.

Vaginal Calculi in a Juvenile Harbor Porpoise (Phocoena phocoena)

A large number of vaginal calculi were observed in a juvenile harbor porpoise (Phocoena phocoena) stranded on Whidbey Island, Washington. Vaginal calculi have been reported in other species, but not in harbor porpoises. Histologic examination of the urinary tract revealed mucosal hyperplasia most likely attributable to the calculi. The calculi were numerous (>30), composed completely of struvite (magnesium ammonium phosphate), and on culture yielded Enterococcus spp., a bacterium not usually associated with struvite urolith formation in domestic animals. The only other lesion of note was severe hepatic lipidosis, and its relationship to the development of the vaginal calculi is unknown.

Disruption of Primary Cilia Induces Gastric Mucosal Hyperplasia

BACKGROUND: Primary cilia are necessary for Hedgehog (Hh) signaling and other pathways. Anterograde ciliary transport is mediated by kinesin-II, a heterotrimeric protein composed of two motor subunits, KIF3A, KIF3B, and a non-motor subunit KAP3. Intraflagellar transport protein 88 (IFT88) participates in protein transport along the cilia. Conventional null mice for KIF3A and IFT88 are not viable. Sonic hedgehog (Shh) is highly expressed in gastric epithelial cells of the corpus compared to the antrum. Therefore we examined the stomach of mice conditionally null for KIF3A and IFT88 to define the role of primary cilia in this organ. METHODS: KIF3A and IFT88 mice harboring one null allele and loxP sites on the other allele on a ROSA26 reporter background were crossed to Shh-Cre mice (KIF3A-/ FL and IFT88-/FL respectively.) KIF3A+/FL, IFT88+/FL, and wild type (WT) littermates were analyzed at 6 and 8 months. Cell lineages were identified by immunohistochemistry in paraffin-sections, and by β-galactosidase (β-gal) staining for the Cre-expressing cells. Acetylated-α-tubulin was used as the marker for cilia. RESULTS: Epithelial cells in the antrum and corpus expressed primary cilia. β-gal staining confirmed variegated glandular Cre expression in all epithelial cells. Gastric epithelial cells did not express cilia in the IFT88-/FL mice, while KIF3A-/FL mice showed reduced numbers of cilia in the corpus versus controls (0.59+0.04 cilia/gland, N=8 vs. 0.72+0.06 cilia/gland, N=14), but no changes in the antrum (0.94+0.05 vs. 1.08+0.09 cilia/gland.) KIF3A-/FL and IFT88-/FL mice exhibited different phenotypes. By 6 months, KIF3A-/FL mice showed mucous pit hyperplasia in the corpus. Mucous neck and zymogenic lineages were not expanded, but parietal cells were still present. The KIF3A-/FL mice phenotype resembled the mucous pit hyperplasia observed in the Shh conditionally null mice generated with H+K+ATPase-Cre. In contrast, the phenotype of the IFT88-/FL mice showed parietal cell atrophy, and proximal corpus hyperplasia due to expansion of the mucous neck cell compartment assessed by TFF2 expression (SPEM) by 4 months of age. We have previously observed that gastrinand ghrelin-secreting cells exhibit primary cilia, but none of the mouse models showed differences in the number of these endocrine cells.CONCLUSION:The IFT88-/FLmice exhibited amore severe phenotype than the KIF3A-/FL mice even though both molecules affect primary cilia function. The phenotype of these two mouse models suggests that Hh signaling is necessary for the maintenance of the corpus epithelium. Also, gastric epithelial cilia might be important for the function but not differentiation of gastrinand ghrelin-secreting cells.

Effect of Oral Insulin on Diabetes-Induced Intestinal Mucosal Growth in Rats

To evaluate the intestinal response to the induction of diabetes and to oral insulin (OI) administration in a rat. Male Sprague-Dawley rats were divided into four experimental groups: control rats, CONTR-INS rats that were treated with OI given in drinking water for 7 days, diabetic rats that were injected with one dose of streptozotocin, and diabetic rats treated with OI. Intestinal structural changes, enterocyte proliferation and enterocyte apoptosis, bax and bcl-2 mRNA and protein levels, insulin receptor expression and ERK protein levels were determined at sacrifice. A one-way ANOVA for comparison, followed by Tukey's test for pair-wise comparison, were used for statistical analysis. Induction of diabetes resulted in a significant increase in bowel and mucosal weight (P < 0.05), mucosal protein (P < 0.05), villus height and crypt depth in jejunum and ileum (P < 0.05), and mucosal DNA in ileum (P < 0.05) (vs. control animals). Diabetes also enhances ERK-induced cell proliferation (P < 0.05) and concomitant bax/bcl-2 induced cell apoptosis (P < 0.05). Treatment of diabetic rats with OI resulted in a significant decrease in jejunal protein content (P < 0.05), jejunal and ileal villus height (P < 0.05), and jejunal crypt depth (P < 0.05), as well as an inhibition of ERK-related cell proliferation in ileum (P < 0.05). Expression of insulin receptor was down-regulated following OI administration in both control and diabetic animals. Experimental STZ-induced diabetes causes intestinal mucosal growth and enhances enterocyte turnover in a rat model. OI administration diminishes diabetes-accelerated cell turnover and diabetes-induced mucosal hyperplasia.

Two cases with nickel-induced oral mucosal hyperplasia: A rare clinical form of allergic contact stomatitis?

Allergic contact stomatitis (ACS) can occur with variable clinical presentations such as erythematous, erosive, and lichenoid forms. Burning mouth symptoms may also be a result of allergic contact stomatitis. Additionally, gingival hyperplasia has been reported in exceptional cases of ACS caused by dental metals. Here, two rare cases are presented of nickel-induced oral mucosal hyperplasia with gingival and upper palatal involvement from metal-porcelain crowns and metal-acrylic upper denture, respectively. In both cases the diagnosis was made on the basis of the positive patch test results to nickel sulfate and the regression of the lesions after removing the nickel containing dental materials. Nickel-induced ACS should be borne in mind in every case of oral mucosal hyperplasia appearing after dental procedures, especially in the presence of previous allergies and sensitization risks such as ear piercing. It might be further suggested to include this variant within the clinical forms of ACS.

Toxic effect of formaldehyde on the respiratory organs of rabbits: A light and electron microscopic study

In this study, the effect of direct exposure of formaldehyde in different concentration was observed in 14 rabbits aged 3-6 months and weighing 1100-1200 g. The animals were divided into two groups with six animals in each group, and two animals were kept as control. The animals of group I were exposed to 10% formalin for 12 weeks and those of group II to 40% formalin solution for 6 weeks. After completion of the experimental periods, the animals were killed and the tissue samples were collected from the nasal cavity, trachea and lungs in 10% neutral buffered formalin and Karnovsky's fixative to examine the histological and electron microscopic changes in the organs. The mucosal cells of nasal cavity showed loss of cilia and epithelial metaplasia was observed in places. There was vascular congestion and mild subepithelial odema. The tracheal epithelium was organized with hyperchromatic nuclei. There was subepithelial odema along with lymphomononuclear cellular infiltration. There was marked emphysema evident as bulla formation of air spaces due to rupture of interalveolar septum. An increased cellularity of alveolar wall was observed, resulting in its thickening. The epithelial lining of bronchioles showed loss of mucosal folds and hyperplasia of cells along with peribronchial lymphomononuclear cellular infiltration. Thickening of wall of blood vessels was evident. Congestion and haemorrhages were observed in places. It is concluded that the histopathological changes were more remarkable in the animals exposed to 40% formaldehyde for short duration than the animals exposed to 10% formaldehyde for longer duration with a more severe effect on the upper part of the respiratory tract than the lower one.

Success and complications associated with placement of fully covered removable self-expandable metal stents for benign esophageal diseases (with videos)

Fully covered esophageal self-expandable metal stents (FCSEMSs) are thought to induce less mucosal hyperplasia and are potentially removable. They may constitute an attractive alternative for the treatment of benign esophageal diseases. To evaluate the efficacy and safety of FCSEMSs in the treatment of benign esophageal diseases. Patients referred for management of benign esophageal disease underwent placement of an FCSEMS and were entered into a prospective database and analyzed retrospectively for clinical response, efficacy, and morbidity. Two tertiary care centers with long-standing experience in the management of benign esophageal strictures. Between January 2006 and September 2007, 35 patients (mean age 61 years, range 20-85 years) underwent FCSEMS placement for benign esophageal diseases at 2 tertiary academic medical centers. There were 19 patients with benign esophageal strictures and 16 patients with leaks/perforations. Temporary placement of FCSEMS until stricture resolution. Clinical response, efficacy, and morbidity. Indications for stent placement were esophageal leak/fistulae (n = 12), refractory benign strictures (n = 10), anastomotic strictures (n = 7), perforations (n = 4), and radiation-induced strictures (n = 2). Immediate complications were chest pain (2 patients), stent migration (2 patients), dysphagia (1 patient), respiratory compromise (1 patient), and arrhythmia (1 patient). Long-term complications included recurrent dysphagia (6 patients), aspiration pneumonia (2 patients), globus sensation (2 patients), abdominal pain (2 patients), and fever (1 patient). Stent migration was observed in 12 patients (34%). After placement, dysphagia scores at 1 month improved significantly from 3.1 ± 1.0 to 1.2 ± 1.3 (P < .0001). A total of 11 of 35 patients (31%) were treated successfully. Specifically, 21% of patients with refractory strictures and 44% of patients with leaks/fistulae had successful long-term outcomes without any need for reinterventions. All stents were retrieved successfully, except for 1 stent, which fractured and was retrieved in 2 pieces without any complications. Use of FCSEMSs for benign esophageal conditions was associated with frequent stent migration and long-term improvement in only one third of patients. Further investigation is required before recommending FCSEMS placement to treat benign diseases of the esophagus and to further characterize the subgroup that might benefit from these interventions.

TNFA deletion alters apoptosis as well as caspase 3 and 4 expression during otitis media

BackgroundTumor necrosis factor (TNFA) is the canonical member of the TNF superfamily, which plays a major role in both inflammation and apoptosis. To evaluate the role of TNFs in otitis media (OM), the most common disease of childhood, we evaluated middle ear (ME) expression of genes encoding the TNF and TNF receptor superfamilies during bacterial OM in the mouse, characterized OM in TNFA-deficient mice, and assessed apoptosis during OM in normal versus TNF-deficient MEs.ResultsTNFs and TNF receptors were broadly regulated during OM, with TNFA showing the highest level of up-regulation. TNF deficient mice exhibited mucosal hyperplasia even in the absence of infection and exuberant growth of the mucosa during OM, including the formation of mucosal polyps. Mucosal recovery during OM was also delayed, in parallel with a delay in mucosal apoptosis and reduced caspase gene expression.ConclusionsThe TNF and TNF receptor superfamilies mediate both inflammation and apoptosis during OM. TNF appears to be critical for the maintenance of mucosal architecture in both the normal and infected ME, since excessive accumulation of mucosal tissue is seen in TNFA-/- MEs both before and after bacterial inoculation of the ME. TNFA is also required for appropriate regulation of caspase genes.

Chronology of The Effect of Massive Small Bowel Resection (MSBR) and Hepatocyte Growth Factor (HGF) on Intestinal Adaptation

Introduction: We have previously shown that hepatocyte growth factor (HGF) significantly increases mucosal protein and DNA content beyond the normal adaptive response at a single timepoint during intestinal adaptation in rats. Also, our previous microarray studies have demonstrated an early emphasis on genes related to mucosal hypertrophy and a later emphasis on genes related to mucosal hyperplasia. This study was designed to correlate the previously identified gene changes with mucosal changes after massive small bowel resection (MSBR) and with the addition of HGF.

Papilloma Formation in Esophagus after Covered Metal Stent Placement: Two Case Reports

Aims: To highlight an uncommon situation during stenting for obesity surgery complications. Place and Duration of Study: 1 st Propaideutic Surgical Unit, Hippokration Hospital, Athens between December 2008 and November 2010. Results: 2 cases of obese patients are presented where the placing of metal stents in esophagogastric region after leakage in the postoperative period of sleeve gastrectomy, resulted in formation of papilloma at the edge of these stents. Conclusion: May be these cases are two of the very few reports in the medical literature which describe mucosal hyperplasia in the esophagus at the edge of a covered metal stent placed for a benign condition.

Comparative Evaluation of the Anti-ulcer Activity of Curcumin and Omeprazole during the Acute Phase of Gastric Ulcer—Efficacy of Curcumin in Gastric Ulcer Prevention against Omeprazole

We have confirmed in our laboratory the antiulcer activity of curcumin during the acute chronic phase of gastric ulcer disease at doses of 20, 40 and 80 mg/kg (dissolved in saline solution). In the previous study, the potent effective dose of curcumin was 80 mg/kg that appears a propitious protective effect against gastric ulcer development. Therefore, the comparison between such recommended dose of curcumin and one of the proton pump inhibitors (PPIs) staff is worth-while. Since, the pharmacological control of gastric acid secretion is the main desired goal for gastro-cytoprotection, particularly, the H+/K+-ATPase (acid proton pump) inhibitors. Nevertheless, several studies have indicated that long-term inhibition of gastric acid secretion results in mucosal hyperplasia and carcinoid tumor development, due to increase circulating gastrin levels. Ulcer and the preventive indexes were scored, mucin, juice volume, total acidity, luminal haemoglobin, total antioxidant and total peroxide were evaluated. The pro-inflammatory cytokine IL-6 and the major angiogenic growth factor VEGF levels were measured. Conclusion, curcumin and omeprazole are potentially preventing gastric lesions development in the gastric wall during the acute phase of gastric ulcer diseases, but curcumin was more potent in its effect. Curcumin promotes gastric ulcer prevention/healing by induction of angiogenesis in the granular tissue of ulcers. That may be via upregulation of VEGF expression as reflected from VEGF level in serum and gastric juice, however, omeprazole might be has no role in this story.

Ultrasonography of normal and abnormal appendix in children

Appendicitis is the most common acute surgical emergency of childhood. Since the original report by Puylaert in 1986, the use of ultrasonography in the diagnosis of appendicitis has been the subject of considerable study. Among the reported diagnostic criteria, the maximal outer diameter (MOD) of the appendix is accepted as the one of the most reliable criteria used to differentiate between a normal appendix and acute appendicitis. However, MOD measurement is subject to inaccuracies because luminal distention by non-compressible, non-inflammatory material such as fecal material, or increased maximal mural thickness due to reactive mucosal lymphoid hyperplasia, or a medical cause due to a generalized gastrointestinal disease, such as Crohn's disease, can cause the measurement to exceed the upper limits of normality. The aim of this article is to introduce the spectrum of ultrasonographic findings in the normal and abnormal appendix and eventually to reduce unnecessary surgery in children.

膵・胆管合流異常を伴った重複胆管に併発した胆嚢過形成粘膜の1例

膵・胆管合流異常を伴った重複胆管に併発した胆嚢過形成粘膜の1例

Toxic effects of a horseradish extract and allyl isothiocyanate in the urinary bladder after 13-week administration in drinking water to F344 rats

Subchronic toxicity of a horseradish extract (HRE), consisting mainly of a mixture of allyl isothiocyanate (AITC) and other isothiocyanates, was investigated with administration at concentrations of 0, 0.0125, 0.025 and 0.05% of HRE in drinking water for 13 weeks to male and female F344 rats. For comparison, treatment with 0.0425% of AITC was similarly performed. Body weight gain was reduced in the 0.05% HRE and AITC males as compared to the 0% controls, and the cause was considered at least partly related to decreased water consumption due to the acrid smell of the test substance and decreased food consumption. Serum biochemistry demonstrated increased urea nitrogen in 0.025 and 0.05% HRE and AITC males and 0.0125-0.05% HRE and AITC females, along with decreased total cholesterol in 0.0125-0.05% HRE females. On histopathological assessment, papillary/nodular hyperplasia of bladder mucosa was observed in 0.05% HRE and AITC males and females, in addition to simple mucosal hyperplasia found in all treated groups. Based on the above findings, no-observed-adverse-effect levels (NOAELs) were estimated to be below 0.0125% of HRE for both males and females, corresponding to 9.4 and 8.0 mg/kg body weight/day, respectively, and there appeared to be comparable toxicological properties of HRE to AITC, such as the inductive effect of significant proliferative lesions in the urinary bladder.

Implications of intestinal metaplasia of the gallbladder in children with pancreaticobiliary maljunction

Pancreaticobiliary maljunction (PBM) is associated with an increased frequency of gallbladder malignancy. Intestinal metaplasia is often observed in gallbladder disease and is a risk factor for gallbladder carcinoma in adults. The hyperplasia-dysplasia-carcinoma progression is one of the possible mechanisms involved in biliary carcinogenesis. In this study, we evaluate the gallbladders of children with PBM for intestinal metaplasia and other histological changes. From January 1997 to July 2010, 45 children with PBM were treated at our institution. A total of 42 children were included in our analysis which included histology and medical record review. The median age was 2.9years (range 1month-16.5years). The most common histological finding was villous-type mucosal hyperplasia, found in 24 patients (57.1%). Mucous gland metaplasia and goblet cell metaplasia were observed in 12 (28.6%) and 7 (16.7%) patients, respectively. There were no cases of malignancy. The intra-gallbladder amylase level in patients with mucosal hyperplasia was significantly elevated (81,373±92,442 vs. 38,932±61,466; p=0.042). Patients with mucous gland metaplasia had significantly higher serum amylase levels (833±1,214 vs. 343±358; p=0.024). The incidence of intestinal metaplasia is relatively high even in children with PBM. Such mucosal changes are related to cholangitis resulting from the regurgitation of pancreatic juice into the bile duct, which also causes hyperamylasemia via cholangio-venous reflux.

Requirement of the Epithelium-specific Ets Transcription Factor Spdef for Mucous Gland Cell Function in the Gastric Antrum

Mucus-secreting cells of the stomach epithelium provide a protective barrier against damage that might result from bacterial colonization or other stimuli. Impaired barrier function contributes to chronic inflammation and cancer. Knock-out mice for the epithelium-specific transcription factor Spdef (also called Pdef) have defects in terminal differentiation of intestinal and bronchial secretory cells. We sought to determine the physiologic function of Spdef in the stomach, another site of significant levels of Spdef expression. We used in situ hybridization and immunohistochemistry to localize Spdef-expressing cells in the mouse stomach; targeted gene disruption to generate mice lacking Spdef; and histologic, immunologic, and transcriptional profiling approaches to determine the requirements of Spdef in stomach epithelial homeostasis. In wild-type mice, Spdef RNA and protein are expressed predominantly in mucous gland cells of the antrum and in mucous neck cells of the glandular corpus. Within 1.5 years, nearly half of homozygous mutant mice developed profound mucosal hyperplasia of the gastric antrum. Submucosal infiltration of inflammatory cells preceded antral hyperplasia by several weeks. The absence of Spdef impaired terminal maturation of antral mucous gland cells, as reflected in reduced expression of Muc6 and Tff2 and reduced numbers of secretory granules. Antral gene expression abnormalities overlapped significantly with those in Spdef(-/-) colon, including genes implicated in secretory granule traffic and functions. Spdef is required for terminal maturation of antral mucous gland cells to protect animals from gastric inflammation and resulting hyperplasia. These requirements parallel Spdef functions in secretory intestinal cells and suggest a common molecular mechanism for maturation of gastrointestinal secretory lineages.

CASE REPORT: Unilateral eyelid lesion and ophthalmologic findings in an aardvark (Orycteropus afer): case report and literature review

To summarize the medical knowledge surrounding aardvarks to date, to describe the ophthalmic examination of a specimen with a chronic history of an upper eyelid lesion, of an assumed blind left eye, and to detail the anesthesia procedure performed. A 23-year-old aardvark was examined under general anesthesia and multiple ocular abnormalities were detected in the left eye (globe deviation, corneal opacities, iridodonesis, and aphakia). A thickening of the palpebral conjunctiva affecting the medial upper eyelid with erosion of the normal eyelid margin anatomy was identified. The adnexal lesion was resected by a wedge resection and histopathology was performed. Suture breakdown 3 days postoperatively required a second surgery, where buried sutures were used. The surgical techniques and postoperative care are discussed. The histopathology revealed mucosal hyperplasia and moderate neutrophilic and lymphoplasmacytic blepharitis. No causal organisms were identified. Following initial wound dehiscence and a modified surgical technique, the upper eyelid healed without complication and retained complete function. The eyelid lesion involved a benign inflammatory and hyperplastic pathology of unknown etiology. Adjusting routine ophthalmic surgical techniques to wildlife and zoo animals can be challenging and complicated. It is important to understand the nature of the animals being managed, their circadian cycle, and habitat, to adjust and individualize the surgical approach, instrumentation, suture material, and perioperative treatment.

Generation of a Transgenic Mouse for Colorectal Cancer Research with Intestinal Cre Expression Limited to the Large Intestine

Genetically modified mice have been used for colon cancer research, but findings from these models are confounded by expression of cancer in multiple organs. We sought to create a transgenic mouse with Cre recombinase (Cre) expression limited to the epithelial cells of the large intestine and used this model to study colon cancer driven by adenomatosis polyposis coli (APC) gene inactivation. A promoter/enhancer from the mouse carbonic anhydrase I gene was used to generate a Cre-expressing transgenic mouse (CAC). After characterizing transgene expression and distribution, CAC mice were crossed to APC(580S) mice to generate mice with APC inactivation at one (CAC;APC(580S/+)) or both alleles (CAC;APC(580S/580S)). Transgene expression was limited to the epithelial cells of the cecum and colon, extended from the crypt base to the luminal surface, and was expressed in approximately 15% of the crypts. No abnormal gross phenotype was seen in 3- or 6-week-old CAC;APC(580S/+) mice, but CAC;APC(580S/580S) mice had significant mucosal hyperplasia in the colon at 3 weeks, which developed into tumors by 6 weeks. By 10 weeks, 20% of CAC;APC(580S/+) mice developed adenomatous lesions in the distal colon (3.0 +/- 0.4 mm; 1.1 per mouse). Dextran sulfate sodium treatment increased the incidence and number of tumors, and this occurred predominantly in distal colon. Our new model has improved features for colon cancer research, that is, transgene expression is limited to the epithelium of the large bowel with normal cells found next to genetically modified cells.