Research Accomplishment Reports 2007

Interpreting Cattle Genomic Data: Biology, Applications and Outreach

J.C. Matthews
Department of Animal and Food Sciences

 

Project Description

The objective (NC1010 Objective 1) of this research is to determine the location, structure, function and expression of genes affecting health, reproduction, production, and product quality in cattle. To determine cellular mechanisms and tissues potentially responsible for enhanced REA and hepatic function of CTC-fed cattle (last year's work), we assessed potential shifts in mRNA expression in the liver and longissimus dorsi (LD) tissues of steers consuming a common finishing diet with or without CTC using the Affymetrix GeneChip (reg. tm) Bovine Genome Array.

Experimental treatments were arranged as a 2 x 2 repeated measures factorial with main effects of added CTC (0 or 350 mg/d) fed for 112 d and tissue (liver and LD collected from the same steer) at harvest (n = 6; CTC (BW = 544 kg) > (P = 0.07) no CTC (BW = 514 kg). Approximately 77% of the probe sets representing 23,000 genes were detected in liver and 70% in LD tissue. CTC treatment altered (P < 0.01) the expression of 142 liver genes (53 up-regulated, 89 down-regulated) and 63 LD genes (36 up-regulated, 27 down-regulated). The genes affected by CTC consumption were subjected to metabolic pathway analysis (INGENUITY Pathways Analysis, Ingenuity Systems, Inc.). The expression of liver mRNA regulated by CTC included those which encode for proteins involved with xenobiotic, LPS/IL-1, alanine, aspartate, and tryptophan metabolism, such that the potential for cell survival, immune system response, and gluconeogenesis was increased. The expression of LD genes regulated by CTC included IGF-I, IL-6, and PI3K/AKT signaling, such that the potential for cell growth and proliferation was increased. These results suggest that the enhanced potential for LD tissue accretion in CTC-fed cattle was supported by an increased potential for glucose production by the liver.

Impact

For the whole project, a number of factors affecting the genetic and molecular basis of variation regarding development and health of the mammary gland, production and quality of milk, feed utilization, rate of growth, and meat quality have been identified. For Kentucky's contribution, a recent goal has been to understand how/why the consumption of chlortetracycline (CTC) by finishing steers increases carcass quality and efficiency of gain. Accompanying the positive attributes of feeding CTC is the concern that feeding antibiotics at sub-therapeutic levels stimulates a reservoir of drug-resistant enteric bacteria, thereby constituting a potential public health risk. Although CTC was originally fed with the goal of reducing deleterious effects of certain species of gut flora on the intestinal mucosa, it is now known that CTC is absorbed by and accumulates in animal tissues.

One way to gain the economic benefits of CTC without its associated health risks would be to identify the proteins/biochemical pathways responsible for improved animal performance so that microflora-inert CTC "mimics" can be developed. Currently, in the United States alone, it is estimated that about 45% of steers and heifers fed for slaughter each year (16 million head) suffer a loss of at least one quality grade from inferior grading of carcasses, whereas the feeding of CTC increases the carcass quality grade by 0.5 units. Therefore, if used, the successful development of a CTC-mimicking compound(s) would add an additional value of $106/hd (based on 2004 prices).

In addition, generation of a database that contains expression profiles of the bovine liver will well-complement existing liver databases of rodents and humans, thus enabling cross species differences and similarities to be discerned. Moreover, within the bovine database, which will reflect CTC-feeding-induced changes, determination of specific biochemical pathways that are altered by CTC exposure, will be revealed and potentially identify targets for therapeutic intervention for both cattle and other mammalian species.

Publications

Kitts, S. E., J. C. Matthews, K. K. Schillo, T. S. Rumsey, T. H. Elasser, S. Kahl, R. L. Baldwin, and K. R. McLeod. 2007. Effects of Chlortetracycline and Synovex-S(reg. tm) on Growth Rate and on Plasma Growth Hormone and Thyroid Hormone Concentrations Following Administration of Thyroid-releasing Hormone and GH-releasing Hormone in Beef Steers. Canadian J. Animal Science 87:327-341.

Liao, S. F., M. J. Alman, E. S. Vanzant, E. D. Miles, D. L. Harmon, K. R. McLeod, J. A. Boling, and J. C. Matthews. 2008. Basal expression of nucleoside transport mRNA differs among small intestinal epithelia of beef steers and is differentially altered by ruminal or abomasal infusion of starch hydrolysate. J. Dairy Science (accepted, manuscript no. JDS-07-0763R1).

Liao, S. F., M. A. Alman, E. S. Vanzant, E. D. Miles, D. L. Harmon, K. R. McLeod, J. A. Boling, and J. C. Matthews. 2007. Ruminal, but not Abomasal Infusion of Starch Differentially Increases Expression of Concentrative Nucleoside Transporter (CNT) mRNA by Small Intestinal (SI) Epithelia of Forage-fed Steers. J. Dairy Science 90 (suppl. 1):343.

Brown, K. R., A. Stromberg, K. C. Chen, J. A. Boling, and J. C. Matthews. 2008. Identification of Chlortetracycline (CTC)-sensitive Pathways in the Liver and Longissimus Dorsi Tissues in Beef Steers Using Microarray Technology. J. Animal Science (accepted, abstract no. 24656).

Matthews, J. C., and K. R. Brown. 2007. Translating Genomics and Proteomics to Applications in Nutrition Programs. Pages 56 to 63 in Proc. 2007 Carolina Feed Industry Swine Nutrition Conference, Research Triangle Park, Raleigh, NC.