Project Number: 6226-32000-008-00
Project Type: Appropriated

Start Date: May 21, 2004
End Date: Jan 31, 2007

Objective:
Our objectives are to identify the cellular and biochemical basis of metabolic diseases in poultry, and identify potential treatment interventions, with respect to: (1) the pathogenesis of tibial dyschondroplasia, and (2) the physiological mechanisms that are involved in host-pathogen interactions in the gastrointestinal tract, and how gut development and competency influence disease resistance.

Approach:
Tibial dyschondroplasia is a leading cause of lameness in poultry. We have developed an experimental model to induce tibial dyschondroplasia (TD) in poultry by feeding chicks and poults thiram, a common dithiocarbamate pesticide, for a short duration of one to two days. This provides us a controllable experimental model to determine the cellular and molecular mechanisms that are affected in the growth plate which cause TD. Employing cellular and biochemical approaches we will study changes in gene expression (by polymerase chain reaction, PCR), and relevant metabolic alterations affecting chondrocyte growth, development, and survival that may be critical to the pathogenesis of TD. We will define events that lead to the broadening of cartilage growth plate and why they fail to differentiate into bone. Using immunochemical approaches we will determine where and how thiram interacts with growth plate cartilage to precipitate such changes. Presuming that many such chemicals are used in poultry houses to control flies, darkling beetles, or as rodent-repellants, or from litter materials that have been pretreated with these chemicals, we will use the above assay model to screen these thiocarbamates to determine if they cause TD and whether some micronutrients can prevent the disease. The gastrointestinal tract performs important metabolic, immunological, and barrier functions in the bird. It is often the first line of defense against potential disease causing agents. Changes in the rate of developmental competency of the GI tract can either enhance or impair disease resistance of the bird. Gastrointestinal developmental competence and dysfunction will be investigated by characterizing the effects of intestinal maturation, function and disease resistance after treatment with prebiotics, probiotics, or combinations of these compounds and microbes (synbiotics). For the first sets of studies we will be screen multiple prebiotics and probiotic cultures alone and in combination (synbiotics) to evaluate their effects on morphologic and immunologic changes in the gut. Identification of synbiotic combinations which accelerate maturation and function will be evaluated further for their ability to improve disease resistence. We will employ proteomics, biochemical, immunochemical and functional genomic technologies in the study of gastrointestinal metabolic disorders.