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OBESITY AND DIABETES: PATHOPHYSIOLOGICAL MECHANISMS AND THERAPEUTIC APPROACHES

Phenotype of Cloned Mice: Development, Behavior, and Physiology

Kellie L.K. Tamashiro^*,, Teruhiko Wakayama, Yukiko Yamazaki, Hidenori Akutsu, Stephen C. Woods^*, Sylvia Kondo, Ryuzo Yanagimachi and Randall R. Sakai^*,1

^* Department of Psychiatry and
Neuroscience Program, University of Cincinnati, Cincinnati, Ohio 45267–0559;
Institute for Biogenesis Research, Department of Anatomy and Reproductive Biology, University of Hawaii School of Medicine, Honolulu, Hawaii 96822; and
Laboratory Animal Services, University of Hawaii, Honolulu, Hawaii 96822

Abstract

Cloning technology has potential to be a valuable tool in basic research, clinical medicine, and agriculture. However, it is critical to determine the consequences of this technique in resulting offspring before widespread use of the technology. Mammalian cloning using somatic cells was first demonstrated in sheep in 1997 and since then has been extended to a number of other species. We examined development, behavior, physiology, and longevity in B6C3F1 female mice cloned from adult cumulus cells. Control mice were naturally fertilized embryos subjected to the same in vitro manipulation and culture conditions as clone embryos. Clones attained developmental milestones similar to controls. Activity level, motor ability and coordination, and learning and memory skills of cloned mice were comparable with controls. Interestingly, clones gained more body weight than controls during adulthood. Increased body weight was attributable to higher body fat and was associated with hyperleptinemia and hyperinsulinemia indicating that cloned mice are obese. Cloned mice were not hyperphagic as adults and had hypersensitive leptin and melanocortin signaling systems. Longevity of cloned mice was comparable with that reported by the National Institute on Aging and the causes of death were typical for this strain of mouse. These studies represent the first comprehensive set of data to characterize cloned mice and provide critical information about the long-term effects of somatic cell cloning.

Key Words: somatic cell cloning • development • obesity • longevity • mouse

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