A previous study has demonstrated that deletion of a region within the last exon bovine growth hormone (bGH) pre-mRNA results in almost complete retention upstream intron (Hampson, R. K., LaFollette, L., and Rottman, F. M. (1989) Mol. Cell. Biol. 9, 1604-1610). We now demonstrate insertion simple purine-rich element (GGAAG), which is present deleted region, activates splicing upon expression transfected cells. Moreover, several repeats GGAA(G) sequence restore to near wild-type levels direct...

In rodents, angiotensin (Ang) II type-1 (AT1) receptors exist as two pharmacologically identical subtypes: AT1a and AT1b. Recent studies have utilized mouse models with specific subtype receptor deletions to differentiate the functional difference between AT1 subtypes. However, little information is available on expression in vasculature. Therefore, this study, −/− mice wild-type littermates (AT1a +/+ ) were used examine its relevance arterial vessels. Using RT-PCR restriction enzyme...

Smooth muscle myosin phosphatase dephosphorylates the regulatory light chain and thus mediates smooth relaxation. The activity of this is dependent upon its myosin-targeting subunit (MYPT1). Isoforms MYPT1 have been identified, but how they are generated their relationship to phenotypes not clear. Cloning middle section chicken rat genes revealed that each gene gave rise isoforms by cassette-type alternative splicing exons. In chicken, a 123-nucleotide exon was included or excluded from...

A fraction of bovine growth hormone (bGH) pre-mRNA undergoes alternative splicing in which the last intron is retained and transported to cytoplasm. Our goal was characterize cis-acting signals bGH that collectively determine distribution between retention. We now demonstrate balance retention cytoplasmic mRNA primarily determined by interaction three degree these deviate from consensus signals. Intron requires presence both suboptimal 5′- 3′-splice sites. Mutation either splice site toward...

Objective A naturally-occurring mutation in cardiac calsequestrin (CASQ2) at amino acid 307 was discovered a highly inbred family and hypothesized to cause Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT). The goal of this study establish causal link between CASQ2D307H the CPVT phenotype using an vivo model.

Adult T-cell leukemia/lymphoma (ATLL) is caused by human T lymphotropic virus type 1 (HTLV-1). Patients with ATLL frequently develop humoral hypercalcemia of malignancy (HHM) resulting from increased osteoclastic bone resorption. Our goal was to investigate the mechanisms ATLL-induced Murine calvaria co-cultured HTLV-1-infected cells directly or conditioned media cell cultures had osteoclast activity that dependent on RANKL, indicating factors secreted a stimulatory effect Factors released...

Feline mammary carcinoma (FMC) is similar to human breast cancer in the late age of onset, incidence, histopathologic features, biological behavior, and pattern metastasis. Therefore, FMC has been proposed as a relevant model for aggressive cancer. The goals this study were develop nude mouse tumor growth metastasis measure expression genes responsible lymphangiogenesis, angiogenesis, progression, lymph node tissues cell lines. Two primary injected subcutaneously, 6 lines into 3 sites...

BACKGROUND The gastrin-releasing peptide receptor (GRPr) is upregulated in early and late-stage human prostate cancer (PCa) other solid tumors of the mammary gland, lung, head neck, colon, uterus, ovary, kidney. However, little known about its role cancer. This study examined effects a heterologous GRPr agonist, bombesin (BBN), on growth, motility, morphology, gene expression, tumor phenotype an osteoblastic canine cell line (Ace-1) vitro vivo. METHODS Ace-1 cells were stably transfected...

Genetically altered mice are increasingly used as experimental models. However, ANG II responses in mouse blood vessels have not been well defined. Therefore, the aim of this study was to determine role regulating major C57/BL6J with isometric force measurements. Our results showed that abdominal aorta induced a concentration-dependent contraction (EC 50 4.6 nM) maximum 75.1 ± 4.9% at 100 nM compared 60 mM K + . Similarly, femoral artery also exhibited contractile response 76.0 3.4%...

Abstract BACKGROUND In 2012, over 240,000 men were diagnosed with prostate cancer and 28,000 died from the disease. Animal models of are vital to understanding its pathogenesis developing therapeutics. Canine in particular useful due their similarities late‐stage, castration‐resistant human disease osteoblastic bone metastases. This study established characterized a novel canine cell line that will contribute pathogenesis. METHODS A (Probasco) was derived mixed breed dog had spontaneous...

BACKGROUND Canine prostate cancer (PCa) is an excellent preclinical model for human PCa. AR‐42 a histone deacetylase inhibitor (HDACi) developed at The Ohio State University that inhibits the proliferation of several cancers, including multiple myeloma, lung, and hepatocellular cancer. In this study, we investigated whether would prevent or decrease. growth metastasis canine PCa (Ace‐1 cells) to bone in vitro vivo. METHODS Proliferation, cell viability, invasion, line (Ace‐1) were measured...

An estimated 10–20 million people worldwide are infected with human T cell leukemia virus type 1 (HTLV-1), endemic areas of infection in Japan, Australia, the Caribbean, and Africa. HTLV-1 is causative agent adult (ATL) associated myopathy/tropic spastic paraparesis (HAM/TSP). expresses several regulatory accessory genes that function at different stages life cycle. The gene Tax-1 required for efficient replication, as it drives transcription viral products, has also been demonstrated to...

Abstract Adult T-cell /lymphomaleukemia (ATLL) is caused by human lymphotropic virus type 1 (HTLV-1). Approximately 80% of ATLL patients develop humoral hypercalcemia malignancy (HHM), a life-threatening complication leading to poor prognosis. Parathyroid hormone–related protein (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) are important factors in the pathogenesis HHM expression PTHrP can be activated nuclear factor κB (NF-κB). NF-κB constitutively cells essential for...

Abstract Background Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult leukemia/lymphoma (ATL) and neurological disorder HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The exact mechanism(s) through which latency disease progression are regulated not fully understood. CCCTC-binding factor (CTCF) an 11-zinc finger, sequence-specific, DNA-binding protein with thousands binding sites throughout mammalian genomes. CTCF has been shown to play a role...

Abstract The domestic cat is an important human companion animal that can also serve as a relevant model for ~250 genetic diseases, many metabolic and degenerative conditions, forms of cancer are analogous to disorders. MicroRNAs (miRNAs) play crucial role in biological processes their dysregulation has significant impact on cellular pathways linked variety diseases. While species already have well-defined characterized miRNAome, miRNAs not been carefully studied cats. As result, there no...

Mice have been increasingly used as models for investigating cardiovascular diseases. However, the responsiveness of mouse vasculature to endothelin (ET)-1 has not clearly established. The goal this study was determine role ET receptors (ETA and ETB) in vessels using isometric force measurements. Results showed that abdominal aorta ET-1 induced a concentration-dependent contraction (EC50: 1.4 nM) with maximum reaching 89.5 ± 4.9% (10 by 60 mM K+ [with nitric oxide synthase (NOS) inhibitor...

Abstract Oral squamous cell carcinoma ( OSCC ) is common in cats and humans invades oral bone. We hypothesized that the cyclooxygenase COX )‐2 inhibitor, meloxicam, with bisphosphonate, zoledronic acid ZOL ), would inhibit tumour growth, osteolysis invasion feline xenografts mice. Human lines expressed ‐1 COX‐2 SCCF2 cells had increased ‐2 mRNA expression bone conditioned medium. Luciferase‐expressing SCCF2Luc were injected beneath perimaxillary gingiva mice treated 0.1 mg kg −1 twice...

Feline oral squamous cell carcinoma (FOSCC) is a highly aggressive head and neck cancer in cats, but the molecular pathogenesis of this still uncertain. In study, p16, p53, pRb proteins were detected quantified by immunohistochemistry forty-three FOSCC primary tumors three xenografts. p16 mRNA levels also measured lines (SCCF1, F2, F3), which consistent with their immunoreactivity. SCCF1 cells had very high protein (55-fold greater) compared to SCCF2 F3. A partial feline cDNA sequence was...

Isoforms of the smooth muscle myosin phosphatase targeting subunit 1 (MYPT1) are generated by cassette-type alternative splicing exons. Tissue-specific expression these isoforms is thought to determine muscle-relaxant properties and unique responses signaling pathways. We used mini-gene deletion/mutation constructs identify cis regulators chicken MYPT1 central exon. Comparisons exon were made between cells fast-phasic contractile phenotype (gizzard), in which skipped, slow tonic (aorta),...

The calcium-sensing receptor (CaR) is responsible for the regulation of extracellular calcium (Ca2+o) homeostasis. CaR activation has been shown to increase proliferation in several cancer cell lines; however, its presence or function never documented lung cancer. We report that Ca2+o-activated results MAPK-mediated stimulation parathyroid hormone-related protein (PTHrP) production human squamous carcinoma (SCC) lines and humoral hypercalcemia malignancy (HHM) vivo. Furthermore, a single...

We are using the tissue-specific splicing of myosin phosphatase targeting subunit (MYPT1) as a model to investigate smooth muscle phenotypic diversity. previously identified U-rich intronic enhancer flanking 5' splice site (IE1), and bipartite exonic enhancer/suppressor, that regulate MYPT1 central alternative exon. Here we show T-cell inhibitor apoptosis (TIA-1) apoptosis-related (TIAR) proteins bind IE1. Co-transfection TIA expression vectors with mini-gene construct increase do not...