Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Transgenic mouse model”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,027 records · Page 57Linked to original sources
PubMed2003

Neuronal overexpression of cyclooxygenase-2 increases cerebral infarction.

Increases in COX-2 enzymatic activity and prostaglandin production have been associated with neuronal injury in both acute and age-related degenerative neurological diseases. In this study, we tested the effects of increased COX-2 activity in a model of transient focal ischemia using a transgenic mouse model in which human COX-2 is constitutively expressed selectively in neurons of the striatum, cerebral cortex, and hippocampus. These COX-2 transgenic mice harbor elevated levels of PGE(2) that are 10-fold higher than nontransgenic levels. A significant increase in infarct volume was observed after middle cerebral artery occlusion with 4 days of reperfusion in COX-2 transgenic mice as compared with nontransgenic littermates. Pretreatment of nontransgenic mice with the selective COX-2 inhibitor SC58236 resulted in a significant reduction of infarct volume in nontransgenic mice, consistent with previous pharmacological studies. However, transgenic COX-2 mice treated with SC58236 did not show a significant reduction. This suggests that chronic increases in COX-2 expression and enzymatic activity, which can occur in aging and in pathological states characterized by oxidative stress and chronic inflammatory processes, can lead to downstream cellular changes that have a negative impact on neuronal survival in cerebrovascular disease.

Animals↗
PubMed2002

Tyr-TGFalpha transgenic mice develop ocular melanocytic lesions.

Transforming growth factor-alpha (TGFalpha) has been implicated in melanocyte transformation, as it is expressed in melanocytic lesions and in melanoma cells. We investigated its role in melanoma development using a transgenic mouse model. The mice were generated by microinjection of a transgene with 270 bp of the mouse tyrosinase promoter and the cDNA for human TGFalpha. No significant skin abnormalities were found, but individuals from three transgenic lines developed ocular melanocytoses (seven out of 10 transgenics), usually after a long latency period. In particular, the melanocyte component of the choroid was thicker than in non-transgenic controls, consistent with hyperplasia. The retinal pigment epithelium was unaffected. Melanocytic lesions were also present in the posterior eye, and abnormal distributions of melanocytes were found in neural tissue of the brain, skeletal muscle of the head and the Harderian glands, indicating migration from the choroid. It was concluded that mice engineered to express the normal growth factor TGFalpha from a tyrosinase promoter spontaneously developed melanocytic lesions in the eye but not the skin.

Animals↗
PubMed2006

Metallothionein-I and -III expression in animal models of Alzheimer disease.

Previous studies have described altered expression of metallothioneins (MTs) in neurodegenerative diseases like multiple sclerosis (MS), Down syndrome, and Alzheimer's disease (AD). In order to gain insight into the possible role of MTs in neurodegenerative processes and especially in human diseases, the use of animal models is a valuable tool. Several transgenic mouse models of AD amyloid deposits are currently available. These models express human beta-amyloid precursor protein (AbetaPP) carrying different mutations that subsequently result in a varied pattern of beta-amyloid (Abeta) deposition within the brain. We have evaluated the expression of MT-I and MT-III mRNA by in situ hybridization in three different transgenic mice models of AD: Tg2576 (carrying AbetaPP harboring the Swedish K670N/M671L mutations), TgCRND8 (Swedish and the Indiana V717F mutations), and Tg-SwDI (Swedish and Dutch/Iowa E693Q/D694N mutations). MT-I mRNA levels were induced in all transgenic lines studied, although the pattern of induction differed between the models. In the Tg2576 mice MT-I was weakly upregulated in cells surrounding Congo Red-positive plaques in the cortex and hippocampus. A more potent induction of MT-I was observed in the cortex and hippocampus of the TgCRND8 mice, likely reflecting their higher amyloid plaques content. MT-I upregulation was also more significant in Tg-SwDI mice, especially in the subiculum and hippocampus CA1 area. Immunofluorescence stainings demonstrate that astrocytes and microglia/macrophages surrounding the plaques express MT-I&II. In general, MT-I regulation follows a similar but less potent response than glial fibrillary acidic protein (GFAP) expression. In contrast to MT-I, MT-III mRNA expression was not significantly altered in any of the models examined suggesting that the various MT isoforms may have different roles in these experimental systems, and perhaps also in human AD.

Alzheimer Disease↗
PubMed2002

Differential vulnerability of cranial motoneurons in mouse models with motor neuron degeneration.

Amyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of selective motoneuron populations, yet it remains unclear why some groups of motoneurons are more vulnerable than others. Our aim was to compare the motoneuron loss in five cranial nuclei at different stages of the disease in three mouse models of ALS: two naturally occurring murine models (progressive motor neuronopathy (pmn) and wobbler) and a transgenic mouse model with a human G93A mutation in the superoxide dismutase-1 (SOD1) gene. By quantifying these different motoneuron populations we report that the degree of degeneration in the various cranial motoneuron nuclei depends on the mouse model and the stage of the disease. The biologically most significant difference between the mutations occurs in the oculomotor/trochlear nucleus which is affected in the pmn mouse but not in the wobbler and SOD G93A mice. These results suggest that there is a selective degeneration of cranial motoneurons in these mouse models as in ALS patients.

Amyotrophic Lateral Sclerosis↗
PubMed1998

Differential patterns of cell cycle regulatory proteins expression in transgenic models of thyroid tumours.

Cell cycle proteins regulate the transitions from G1 to S and G2 to M phases. In higher eukaryotes, their function is controlled by intracellular cascades regulated by extracellular growth factors. We have studied in previously described transgenic mouse models for thyroid proliferative diseases the expression of the key proteins regulating the cell cycle by Western blotting and immunohistochemistry, and have correlated the observations with the known actions of the transgenes on the signal transduction cascades. In the adenosine A2a receptor model, the cyclic AMP pathway, upstream of the Rb family cell division block, is constitutively activated. In the model expressing HPV 16 E7 protein, the Rb-like proteins are inhibited. Cyclin-dependent kinases cdk4, cdk2 and cdc2, and the associated cyclins D, E and A have been studied. Cyclin D3 appears as the major cyclin D subtype expressed in mouse thyroid epithelial cells in normal and transgenic mice. In the adenosine A2aR model, all cell cycle proteins tested were accumulated. In the E7 model, all cell cycle proteins except for D-type cyclins and cdk4 were also accumulated. A similar pattern was observed in thyroids coexpressing both transgenes, suggesting a dominant effect of E7 over the consequences of the cAMP cascade activation. The cyclin-dependent kinase inhibitors p21cip1/waf1 and p27kip1 were not downregulated in these proliferating thyroids which suggest other roles than the inhibition of the cell cycle progression.

Animals↗
PubMed2001

Apoptosis and chemoresistance in transgenic cancer models.

Multidrug resistance remains an unresolved problem in clinical oncology. Over a decade ago genes encoding cellular efflux pumps were shown to confer resistance to a broad spectrum of biochemically unrelated anticancer drugs even before the compounds reached their intracellular targets. More recently it has become apparent that many drugs induce a common apoptotic program, such that mutations in this program can also produce multidrug resistance. However, a thorough evaluation of the contribution of apoptotic defects to this "postdamage" drug resistant phenotype is technically complicated, and this has led to uncertainty about the overall significance of apoptosis in therapy-induced cell death. For example, correlative analyses using patient specimens are limited by unknown background mutations in the biopsy material, and assays using cancer cell lines can be biased by unphysiological conditions. We sought to circumvent these restrictions by utilizing a tractable transgenic cancer model to examine the impact of apoptosis on treatment outcome. Here we discuss potential caveats of cell culture based assays, highlight features of genetically engineered mice as potential model systems, and describe a tractable transgenic mouse model to study drug responses in a series of primary lymphomas with genetically defined lesions treated at their natural site.

Animals↗
PubMed2005

Making better transgenic models: conditional, temporal, and spatial approaches.

Over the last decade transgenic mouse models have become a common experimental tool for unraveling gene function. During this time there has been a growing expectation that transgenes resemble the in vivo state as much as possible. To this end, a preference away from heterologous promoters has emerged, and transgene constructs often utilize the endogenous promoter and gene sequences in BAC, PAC and YAC form without the addition of selectable markers, or at least their subsequent removal. There has been a trend toward controlled integration by homologous recombination, either at a characterized chromosomal localization or in some cases within the allele of interest. Markers such as green fluorescent protein (GFP), beta-galactosidase (LacZ), and alkaline phosphatase (AP) continue to be useful to trace transgenic cells, or transgene expression. The development of technologies such as RNA interference (RNAi), are introducing new ways of using transgenic models. Future developments in RNAi technology may revolutionize tissue specific inactivation of gene function, without the requirement of generating conditionally targeted mice and tissue specific recombinase mice. Transgenic models are biological tools that aid discovery. Overall, the main consideration in the generation of transgenic models is that they are bona fide biological models that best impart the disease model or biological function of the gene that they represent. The main consideration is to make the best model for the biological question at heart and this review aims to simplify that task somewhat. Here we take a historical perspective on the development of transgenic models, with many of the important considerations to be made in design and development along the way.

Animals↗
PubMed2004

Spontaneous and controllable activation of suicide gene expression driven by the stress-inducible grp78 promoter resulting in eradication of sizable human tumors.

GRP78 is a stress-inducible chaperone protein with antiapoptotic properties that is overexpressed in transformed cells and cells under glucose starvation, acidosis, and hypoxic conditions that persist in poorly vascularized tumors. Previously we demonstrated that the Grp78 promoter is able to eradicate tumors using murine cells in immunocompetent models by driving expression of the HSV-tk suicide gene. Here, through the use of positron emission tomography (PET) imaging, we provide direct evidence of spontaneous in vivo activation of the HSV-tk suicide gene driven by the Grp78 promoter in growing tumors and its activation by photodynamic therapy (PDT) in a controlled manner. In this report, we evaluated whether this promoter can be applied to human cancer therapy. We observed that the Grp78 promoter, in the context of a retroviral vector, was highly activated by stress and PDT in three different types of human breast carcinomas independent of estrogen receptor and p53. Complete regression of sizable human tumors was observed after prodrug ganciclovir treatment of the xenografts in immunodeficient mice. In addition, the Grp78 promoter-driven suicide gene is strongly expressed in a variety of human tumors, including human osteosarcoma. In contrast, the activity of the murine leukemia virus (MuLV) long-terminal repeat (LTR) promoter varied greatly in different human breast carcinoma cell lines, and in some cases, stress resulted in partial suppression of the LTR promoter activity. In transgenic mouse models, the Grp78 promoter-driven transgene is largely quiescent in major adult organs but highly active in cancer cells and cancer-associated macrophages, which can diffuse to tumor necrotic sites devoid of vascular supply and facilitate cell-based therapy. Thus, transcriptional control through the use of the Grp78 promoter offers multiple novel approaches for human cancer gene therapy.

Animals↗
PubMed2001

p53 deficiency alters the yield and spectrum of radiation-induced lacZ mutants in the brain of transgenic mice.

Exposure to heavy particle radiation in the galacto-cosmic environment poses a significant risk in space exploration and the evaluation of radiation-induced genetic damage in tissues, especially in the central nervous system, is an important consideration in long-term manned space missions. We used a plasmid-based transgenic mouse model system, with the pUR288 lacZ transgene integrated in the genome of every cell of C57Bl/6(lacZ) mice, to evaluate the genetic damage induced by iron particle radiation. In order to examine the importance of genetic background on the radiation sensitivity of individuals, we cross-bred p53 wild-type lacZ transgenic mice with p53 nullizygous mice, producing lacZ transgenic mice that were either hemizygous or nullizygous for the p53 tumor suppressor gene. Animals were exposed to an acute dose of 1 Gy of iron particles and the lacZ mutation frequency (MF) in the brain was measured at time intervals from 1 to 16 weeks post-irradiation. Our results suggest that iron particles induced an increase in lacZ MF (2.4-fold increase in p53+/+ mice, 1.3-fold increase in p53+/- mice and 2.1-fold increase in p53-/- mice) and that this induction is both temporally regulated and p53 genotype dependent. Characterization of mutants based on their restriction patterns showed that the majority of the mutants arising spontaneously are derived from point mutations or small deletions in all three genotypes. Radiation induced alterations in the spectrum of deletion mutants and reorganization of the genome, as evidenced by the selection of mutants containing mouse genomic DNA. These observations are unique in that mutations in brain tissue after particle radiation exposure have never before been reported owing to technical limitations in most other mutation assays.

Animals↗
PubMed2003

The use of genetically altered mice for breast cancer prevention studies.

Chemoprevention through nutritional and dietary changes may offer an important means of inhibiting the development and progression of breast cancer, which would have a major impact on public health. Studies to assess the efficacy of potential chemopreventive compounds are difficult to perform in large human populations, whereas the use of genetically engineered mice (GEM) for preclinical testing offers several advantages. GEM models can be utilized to assess the inhibitory effects of nutritional and chemopreventive agents on well-defined oncogenic signaling pathways. Because several transgenic mouse models progress through a well-defined temporal series of stages leading to invasive carcinoma formation, they may be particularly useful for determining cancer stage-specific responses to nutritional and chemopreventive agents. The C3(1)SV40 T/t-antigen transgenic mouse mammary cancer model has been utilized for chemopreventive research in which mammary tumors develop over a well-characterized time course. Several compounds have been shown to inhibit mammary tumor development in this model, including retinoids, di-fluoromethylornithine (DFMO), dehydroepiandrosterone (DHEA), antiangiogenic compounds and nonsteroidal antiinflammatory drugs (NSAID). All of the chemopreventive agents used in the C3(1)Tag mammary mouse model appear to affect the promotion stage of tumorigenesis, suggesting that these agents may be useful in inhibiting the transition of human ductal carcinoma in situ (DCIS) to invasive carcinoma. Selective combinations of chemopreventive agents may be particularly useful for targeting multiple signaling pathways involved in cancer development and progression leading to improved clinical responses. The application of gene expression profiling to chemopreventive studies will aid in the selection of appropriate models for preclinical testing and further define mechanisms of action.

Animals↗
PubMed1997

Repression of vasopressin gene expression by glucocorticoids in transgenic mice: evidence of a direct mechanism mediated by proximal 5' flanking sequence.

Glucocorticoids are known to exert multiple effects upon neuronal systems and neuronal gene expression but the molecular mechanisms through which these effects are mediated are largely undefined. In this study, a transgenic mouse model that expresses a bovine vasopressin transgene was used to investigate the mechanisms by which this neuropeptide gene is repressed by glucocorticoids. Using both northern analysis and a reverse transcriptase polymerase chain reaction assay, depletion of glucocorticoids with the 11,beta-hydroxylase inhibitor metyrapone was shown to result in a dexamethasone-reversed increase in ectopic adrenal transgene messenger RNA levels. This result shows that sequences within the confines of the 3.5 kb transgene are sufficient to mediate repression by glucocorticoids, and indicates the involvement of a type II glucocorticoid receptor mechanism which is independent of cellular context. Evidence for the involvement of cis-acting repressive elements in the proximal 5' flanking sequence was obtained in further studies in which bovine transgene constructs were shown to be negatively regulated by dexamethasone in 293 cells. The further demonstration that recombinant glucocorticoid receptor binds to a vasopressin promoter fragment in an in vitro electrophoretic mobility shift assay provided additional evidence of a direct mechanism of repression. Both in vitro studies were consistent with the presence of a glucocorticoid regulatory element within the region -300 to 155 of the transcription start site. The use of an in vivo transgenic system combined with in vitro analyses of gene promoter fragments enabled the characterization of the molecular mechanisms which effect physiological changes in vasopressin gene expression, and provided evidence of a direct mechanism of repression mediated by sequences within the vasopressin gene promoter.

Animals↗
PubMed2003

Amelioration of nephropathy in mice expressing HIV-1 genes by the cyclin-dependent kinase inhibitor flavopiridol.

Cumulative evidence suggests that human immunodeficiency virus-associated nephropathy (HIVAN), the third leading cause of end-stage renal disease in African-Americans, may respond to therapeutic strategies that interrupt HIV-1 expression in infected renal epithelium. We recently demonstrated that suppression of HIV-1 transcription in infected glomerular visceral epithelial cells by flavopiridol, a small-molecule inhibitor of the cyclin-dependent kinases required for HIV-1 promoter activity, reversed HIV-induced proliferation and dedifferentiation in vitro. To address whether flavopiridol could ameliorate HIV-induced renal disease, we utilized a well-established HIV-1 NL4-3 transgenic mouse model of HIVAN. HIV-1 proviral transgene expression in whole kidney was markedly suppressed by a 20 day treatment with flavopiridol. Following treatment, histopathological, serological and urinary indices of nephrosis were normalized in flavopiridol-treated but not in vehicle-treated transgenics. Microarray analysis showed that 82% of the dysregulated genes in HIVAN kidney were normalized to control levels by flavopiridol, whereas continued dysregulation of most of the remaining 18% was attributable to an effect from flavopiridol alone. These results demonstrate for the first time that targeting the cyclin-dependent kinases that support HIV-1 expression can ameliorate HIV-induced disease in an animal model.

AIDS-Associated Nephropathy↗
PubMed2004

Alveolar rhabdomyosarcomas in conditional Pax3:Fkhr mice: cooperativity of Ink4a/ARF and Trp53 loss of function.

Alveolar rhabdomyosarcoma is an aggressive childhood muscle cancer for which outcomes are poor when the disease is advanced. Although well-developed mouse models exist for embryonal and pleomorphic rhabdomyosarcomas, neither a spontaneous nor a transgenic mouse model of alveolar rhabdomyosarcoma has yet been reported. We report the first mouse model of alveolar rhabdomyosarcoma using a conditional Pax3:Fkhr knock-in allele whose activation in late embryogenesis and postnatally is targeted to terminally differentiating Myf6-expressing skeletal muscle. In these mice, alveolar rhabdomyosarcomas occur but at low frequency, and Fkhr haploinsufficiency does not appear to accelerate tumorigenesis. However, Pax3:Fkhr homozygosity with accompanying Ink4a/ARF or Trp53 pathway disruption, by means of conditional Trp53 or Ink4a/ARF loss of function, substantially increases the frequencies of tumor formation. These results of successful tumor generation postnatally from a target pool of differentiating myofibers are in sharp contrast to the birth defects and lack of tumors for mice with prenatal and postnatal satellite cell triggering of Pax3:Fkhr. Furthermore, these murine alveolar rhabdomyosarcomas have an immunohistochemical profile similar to human alveolar rhabdomyosarcoma, suggesting that this conditional mouse model will be relevant to study of the disease and will be useful for preclinical therapeutic testing.

ADP-Ribosylation Factors↗
PubMed2000

A physiological ligand of positive selection is seen with high specificity.

Positive selection is a process that ensures that peripheral T cells express TCR that are restricted to self-MHC molecules. This process requires both self-MHC and self-peptides. We have recently established a TCR transgenic mouse model (C10.4 TCRtrans+) in which the transgenic TCR was selected on the nonclassical MHC class Ib molecule H2-M3 in conjunction with a physiologically occurring peptide derived from the mitochondrial NADH-dehydrogenase subunit 1 gene (9-mer peptide). Here, the specificity of positive selection of C10.4 TCRtrans+ T cells was examined using a fetal thymic organ culture system. We demonstrated that at low peptide concentrations, shortening the NADH-dehydrogenase subunit 1 gene 9-mer peptide or mutating its surface-exposed side chains severely impaired its ability to induce positive selection. We concluded that under physiological conditions positive selection of C10.4 TCRtrans+ T cells was highly specific and occurred at low epitope densities.

Animals↗
PubMed2000

Multiepitopic HLA-A*0201-restricted immune response against hepatitis B surface antigen after DNA-based immunization.

CTL together with anti-envelope Abs represent major effectors for viral clearance during hepatitis B virus (HBV) infection. The induction of strong cytotoxic and Ab responses against the envelope proteins after DNA-based immunization has been proposed as a promising therapeutic approach to mediate viral clearance in chronically infected patients. Here, we studied the CTL responses against previously described hepatitis B surface Ag (HBsAg)-HLA-A*0201-restricted epitopes after DNA-based immunization in HLA-A*0201 transgenic mice. The animal model used was Human Human D(b) (HHD) mice, which are deficient for mouse MHC class I molecules (beta(2)-microglobulin(-/-) D(b-/-)) and transgenic for a chimeric HLA-A*0201/D(b) molecule covalently bound to the human beta(2)-microglobulin (HHD(+/+)). Immunization of these mice with a DNA vector encoding the small and the middle HBV envelope proteins carrying HBsAg induced CTL responses against several epitopes in each animal. This study performed on a large number of animals described dominant epitopes with specific CTL induced in all animals and others with a weaker frequency of recognition. These results confirmed the relevance of the HHD transgenic mouse model in the assessment of vaccine constructs for human use. Moreover, genetic immunization of HLA-A2 transgenic mice generates IFN-gamma-secreting CD8(+) T lymphocytes specific for endogenously processed peptides and with recognition specificities similar to those described during self-limited infection in humans. This suggests that responses induced by DNA immunization could have the same immune potential as those developing during natural HBV infection in human patients.

Alleles↗
PubMed2001

Evaluation of phospholipid transfer protein and cholesteryl ester transfer protein as contributors to the generation of pre beta-high-density lipoproteins.

High-density lipoproteins (HDLs) are considered anti-atherogenic because they mediate peripheral cell cholesterol transport to the liver for excretion and degradation. An important step in this reverse cholesterol-transport pathway is the uptake of cellular cholesterol by a specific subclass of small, lipid-poor apolipoprotein A-I particles designated pre beta-HDL. The two lipid-transfer proteins present in human plasma, cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP), have both been implicated in the formation of pre beta-HDL. In order to investigate the relative contribution of each of these proteins, we used transgenic mouse models. Comparisons were made between human CETP transgenic mice (huCETPtg), human PLTP transgenic mice (huPLTPtg) and mice transgenic for both lipid-transfer proteins (huCETPtg/huPLTPtg). These animals showed elevated plasma levels of CETP activity, PLTP activity or both activities, respectively. We evaluated the generation of pre beta-HDL in mouse plasma by immunoblotting and crossed immuno-electrophoresis. Generation of pre beta-HDL was equal in huCETPtg and wild-type mice. In contrast, in huPLTPtg and huCETPtg/huPLTPtg mice, pre beta-HDL generation was 3-fold higher than in plasma from either wild-type or huCETPtg mice. Our findings demonstrate that, of the two plasma lipid-transfer proteins, PLTP rather than CETP is responsible for the generation of pre beta-HDL. These data support the hypothesis of a role for PLTP in the initial stage of reverse cholesterol transport.

Animals↗
PubMed1998

Evaluation and validation issues in the development of transgenic mouse carcinogenicity bioassays.

Transgenic mouse models have emerged as plausible alternatives to long-term bioassays for carcinogenicity. Three transgenic lines evaluated to date have shown a clear capability to discriminate between carcinogens and noncarcinogens, using long-term bioassay results as the standard. The data also suggest that the transgenic lines will not fully duplicate long-term bioassay results. It is proposed that these models do not respond to chemicals that have induced highly restricted species or strain-specific tumor responses in mice or rats. Rather, the value of the transgenic models is predicated on a preferential response to transspecies carcinogens (i.e., those positive in both rats and mice, often including tumors in the same tissues). Thus, although results in transgenic models may not be completely concordant with long-term bioassays, the data can be used effectively in chemical and drug safety assessments. Further, it is proposed that validation of the models is readily achievable via ongoing studies. Validation of any alternative model is best achieved by sufficient mechanistic understanding of the model to reasonably predict the outcome of bioassays conducted in the models and use all available information on the drug or chemical. This goal can now be met with the transgenic mouse lines.

Animal Testing Alternatives↗
PubMed2002

TGFbeta induces morphological and molecular changes similar to human anterior subcapsular cataract.

BACKGROUND: Transforming growth factor beta (TGFbeta) has been shown to induce subcapsular plaques in cultured rat lenses as well as in lenses of transgenic mice. In the present study the authors have extended their analysis of these cataract models to determine how closely they mimic human cataract. In particular, they studied the maturation of cataract in the transgenic model to determine if it develops similar features as previously described for anterior subcapsular cataract (ASC) in humans. Furthermore, they investigated whether both of these animal models express the range of molecular markers that have now been shown to be present in human ASC. METHODS: Histology and periodic acid Schiff staining were used to study the development and maturation of subcapsular plaques in transgenic mice overexpressing TGFbeta1 in the lens. Immunolabelling methods were used to identify the molecular markers for ASC in both the transgenic mouse model and in rat lenses cultured with TGFbeta2. RESULTS: Histological analysis showed that the subcapsular plaques that develop in adult transgenic mouse lenses bear a striking similarity to mature human ASC, including the formation of a new epithelial-like layer extending between the subcapsular plaque and the underlying fibre mass. All known molecular markers for human ASC were induced in both rodent models, including collagen types I and III, tenascin, and fibronectin. They also identified the presence of desmin in these plaques, a putative novel marker for human cataract. CONCLUSIONS: In both transgenic mouse and rat lens culture models TGFbeta induces markers similar to those found in human ASC. Atypical expression of these cataract markers is also characteristic of posterior capsular opacification (PCO). The molecular markers expressed are typical of a myofibroblastic/fibroblastic phenotype and suggest that a common feature of ASC and PCO may be induction of an epithelial-mesenchymal transition by TGFbeta.

Animals↗