Abstract

The advent of animal models of pediatric surgical diseases has not only allowed us to study the etiology and pathogenesis of complex congenital anomalies but has also led to major advances in the surgical and therapeutic management of these conditions. Even though representative animal models do not exist for every human disease, the animal models available to us today are still of great importance for medical research. Animal models allow us to comprehend the molecular and biochemical basis of diseases, and possibly find new drugs and forms of therapy, both medical and surgical. Different animal models have been and may be used. Because of their easy availability, smaller animals such as rodents are often preferred as models. Mice (Mus musculus) offer many advantages. They are similar to humans in a biological and genetic manner, so that much, but not all, of the knowledge gained from studies in mice may be applied to humans. The genome of the mouse is similar to the human genome, with regard to the size and number of genes. Mice have a very high reproduction rate, a short life span and mature quickly. This makes it possible to easily follow the effects of changed genes over many generations. At the present time, mice have become the most important and common animal models for human diseases. For many years the mouse genome has been closely investigated, and many mutations, which have either spontaneously developed in a population or were induced through outer influences ( for example chemical mutagenesis) have been demonstrated. Many international co-operations work on methods of describing the function of each single genome with different strategies. Rats ( Rattus norvegicus) are also widely used in research, as they are particularly suitable for physiological, pharmacological and behavioral research. They have also contributed greatly to research involving surgical techniques and the study of many teratogens. Animal models are of great importance for the analysis of genes. With their help it is possible to set up models for the examination of gene expression and gene regulation. Genes may be specifically inactivated within animals (knockout model), and the effect on the organism can be studied. By inserting an additional recombinant gene (transgenic animal model), its expression and influence on the metabolism of the organism can be examined. The setting up of expression analysis is only part of solving the functions of genes in an organism or in tissues. Since genes generally work in coordination, thus de. ning the characteristics of an organism, it is necessary to examine the function of the genes in connection with the organism under physiological conditions. Broadly speaking, there are four main types of animal models in use today: naturally occurring, teratogen induced, surgically created and transgenic animals. Obviously, the animals in which diseases occur naturally are the ideal models with which to study disease pathogenesis, as there is little or no interference to the animal prior to the study. The ground-breaking development of transgenic animals has not only allowed researchers to almost mimic the natural occurrence of certain conditions but also gives insight into the specific genes involved in the regulation of the disease process and how their modi. cation might alter the course of the disease. Teratogen-induced models, although useful, have the drawback of exposing the animal to a generalized noxious stimulus, which can result in widespread detrimental effects rather than simply targeting a specific organ system. Finally, surgical models can closely simulate surgical procedures and conditions found in human neonates but difficulties may arise in relation to controlling variables such as anesthesia, analgesia, sepsis and feeding. Following from these models, research has sought to develop potential therapeutic approaches, including surgical interventions, which can be employed in the management of many conditions, and as a result many different models for several important human diseases have been developed over many years of pediatric surgical research. Lesser known animal models not discussed in this review include those for spina bifida (curly tail and delayed splotch mouse models, surgical rat and lamb models), hydrocephalus (HTX rat, HSV and L1 knockout mouse models), cloacal exstrophy ( suramin chick and surgical lamb model), cryptorchidism (Insulin-3 and HOXA 11 knockout mice, flutamide rat, surgical rat and rabbit models), biliary atresia ( rotavirus mouse model), necrotizing enterocolitis (hypoxia/lipopolysaccharide and casein piglet model, surgical rabbit model, hypoxic rat model), short bowel syndrome (surgical mouse model), vesico-ureteral reflux (surgical piglet model) and pyloric stenosis (mutant hph-1 mouse model). Research into important and challenging neonatal conditions such as gastroschisis (GS), Hirschsprung's disease (HD), VACTERL association and congenital diaphragmatic hernia (CDH) has been greatly advanced by the ready availability of animal models and will form the basis of the discussion in this review.