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Identification of the genes for a human disease provides significant insights into the molecular mechanism underlying the pathogenesis of the disease. A human disease gene can be identified by its chromosomal location (positional cloning). Linkage analysis is a key step in positional ...

Disorders of the cardiovascular system are often caused by the interaction of genetic and environmental factors that jointly contribute to individual susceptibility. Genomic data and bioinformatics tools generated from genome projects, coupled with functional verificat ...

Variance component linkage analysis has become one of the most popular tools for the analysis of polygenic phenotypes. In particular for cardiovascular disease, such as coronary artery disease and myocardial infarction, variance component analysis holds some unique advantages. ...

Positional cloning is a comprehensive genetic strategy used to identify a disease-causing gene without any prior knowledge of the pathogenesis or protein defects involved in the disease process. The basic process involves collection of accurately diagnosed patients and their fam ...

To permit long-term measurement of time-dependent changes in levels of dialyzable drugs and transmitters in the spinal intrathecal (IT) space of the unanesthetized rat, we developed a dialysis catheter for chronic placement. This was accomplished by constructing a loop-flexible pr ...

Vincristine belongs to the family of vinca alkaloids used for treatment of malignant tumors. Clinical application of these agents is often associated with dose-dependent painful neuropathy due to damages to the peripheral axons. A rat model of vincristine-induced hyperalgesia was d ...

Peripheral nerve damage involves inflammation, and is frequently causal to the development of neuropathic pain. However, inflammatory neuropathies often occur in the absence of trauma. We have recently developed an animal model of neuropathic pain where allodynia is induced by nerve ...

The procedures to induce insulin-deficient diabetes in rats using streptozotocin are described along with a number of insulin treatment regimes that can be used to maintain these animals at different degrees of glycemia for periods of weeks to months. Streptozotocin-diabetic rats de ...

Partial sciatic nerve transection (PST) of the sciatic nerve of rats and mice is described as a model of painful neuropathy. The rationale for developing this model was to establish a simple partial nerve injury without application of foreign material. In contrast to the frequently used model of ...

Since its introduction in 1992, the spinal nerve ligation (SNL) model of neuropathic pain has been widely used for various investigative works on neuropathic pain mechanisms as well as in screening tests for the development of new analgesic drugs. This model was developed by tightly ligating ...

The purpose of this chapter is to provide guidance to the novice investigator as to two models of ongoing nociception in rats. The models described herein are the formalin test, in which an irritant is injected subcutaneously into a dorsal paw and the numbers of flinches produced over 60 min are counte ...

Phosphoinositides are a family of minor membrane phospholipids that have important roles in cell signaling pathways. Seven phosphoinositides have been identified in eukaryotic cells (all are found in 3T3-L1 cells), including phosphatidylinositol 3-phosphate , phosphatid ...

Animal models of type 1 diabetes provide excellent tools for investigators to evaluate the pathogenesis, metabolic effects, and complications of type 1 diabetes. These models have many features of human type 1 diabetes with some important exceptions that will be pointed out in this chapter. ...

The proper functioning of the insulin-producing β-cells in the pancreas depends on the action of various proteins whose function and level of expression are tightly regulated in order to maintain a well state. Alterations in these processes can lead to diseased states such as diabetes melli ...

Insulin gene expression levels can be detected and quantified using a broad range of molecular biology techniques. Traditionally, detection of insulin mRNA levels in both β-cell lines and purified islets has been performed by Northern blot analysis, using the full-length insulin cDNA as a ...

Detection of insulin by immunocytochemistry is one of the most powerful and sensitive techniques available to monitor levels of expression in islets (1), β-cells in culture (2), tissue samples (3), and cells transgenically expressing the insulin gene (4). Like all immunocytochemistry t ...

The long-term complications associated with diabetes such as heart disease, kidney failure, blindness, and limb amputations are mostly the result of chronic elevations in blood glucose levels, also known as chronic hyperglycemia (1,2). The exact molecular mechanisms by which hyperg ...

Preparation of plasma membrane (PM) sheets from intact cells is a simple method for obtaining an immobilized cytoplasmic PM surface that can be probed with antibodies or chemical probes. This method was first reported by Robinson et al. (1) who used it to detect the presence of the GLUT-4 glucose tran ...

In 1980, two groups simultaneously provided evidence of the existence of an intracellular pool of glucose transporters in rat adipocytes (1,2). We now know that facilitative glucose uptake occurs through a family of highly related integral membrane proteins that share significant seq ...

Numerous growth factors, hormones, and transforming oncogenes activate phosphatidylinositol 3-kinase (PI3K), an enzyme that phosphorylates the 3′-hydroxyl position of phosphoinositides to generate the intracellular messengers phosphatidylinositol-3-phosp ...