Date of Award

2004

Level of Access Assigned by Author

Campus-Only Thesis

Degree Name

Master of Science (MS)

Department

Animal Sciences

Advisor

James Weber

Second Committee Member

Robert Causey

Third Committee Member

Ken Andries

Abstract

Unless treated, congenital hypothyroidism causes severe mental retardation, stunted physical development, and perceptual and motor disabilities. Thyroid hormone is essential for normal brain development during gestation and infancy. Clinical studies indicate that adults treated for hypothyroidism during infancy can still suffer permanent cognitive impaimlents, as seen with below average IQ scores and spatial learning disabilities. The hytlhyt mouse is a rodent model for genetically induced fetal hypothyroidism which affords a means of investigating the somatic, behavioral, and neuroanatomical aspects of this disorder. The present study purported to characterize the hyt/hyt mouse in terms of its long term somatic, behavioral and cognitive development and then examining the reversibility of hypothyroidism and developmental changes in these mice. Thyroxin supplemented hyt/+ mothers and hytlhyt fathers were mated to yield hytlhyt (hypothyroid) and hyt/+ (euthyroid) offspring. Polymerase chain reaction (PCR) analysis was done on tail clippings taken from the mice to determine their genetic make-up. A +I+ (genetically normal, BalbIcBYJ) comparison group was derived from a strain of standard laboratory mouse. A total of 195 subjects were assessed for physical growth, reflexive development, and spatial learning. The grip strength meter was adapted to the mouse for this study. The results showed that even though the hytlhyt mouse was receiving triodothyronine (T3) supplemented in their water, they were significantly impaired when compared with BalbIcBYJ (euthyroid) controls. The hytlhyt mice had reduced physical size and growth, delayed eye opening and ear raising, and deficient spatial learning. The hytlhyt mouse's utility as a rodent model of congenital hypothyroidism was confirmed by the similarity of these findings to other rodent models. This finding reinforced the assumption of genetic thyroid deficiency in the hytlhyt mouse. The grip strength meter was successfully adapted to mice. The combined use of hytlhyt mouse with the grip strength may offer a tool for future studies that are successful at reversing congenital hypothyroidism in-utero and understanding the biological underpinnings of this disorder.

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