title: The response of transgenic mice to beta-adrenergic agonist administration is different from that of normal mice.
abstract: Eighteen transgenic mice carrying an ovine metallothionein la-ovine growth hormone (oMTla-oGH) transgene and 18 littermate normal mice were used to investigate the effects of transgene expression and clenbuterol administration on growth performance and skeletal muscle characteristics. The oGH transgene was activated from 21 d of age, and half of the mice were fed 15 ppm clenbuterol from 42 to 70 d of age. All mice were killed at 70 d of age after 4 wk of treatment, and organs and muscles were dissected, weighted, and analyzed. Transgenic mice (TM) gained 2.6 times more than normal mice (NM). However, TM had a significantly lower (-20%, P < .01) proportion of muscle, expressed as percentages of body weights, and a higher percentage of heart (+10%), liver (+26%, P < .01) and spleen (+64%, P < .01) than NM. Clenbuterol improved the weight gain of TM by 20%, compared with 10% for NM. The growth-promoting effect of clenbuterol was almost exclusively confined to skeletal muscle (24% increase) in NM, in contrast to a more generalized growth increase in all tissues including skeletal muscle (11% increase) in TM. The skeletal muscles of TM were longer but smaller in diameter due to 30% smaller muscle fiber cross-sectional area. Clenbuterol increased the muscle fiber size of all fiber types by 60% in NM, compared to 30% in TM. Muscle DNA concentrations and content were higher (P < .05) in TM than in NM, and clenbuterol administration decreased DNA concentrations but not total DNA content for both genotypes. Cathepsin B, C, and H activities were higher (P < .01) in TM muscle, but the significance is not clear at the present time, although it points to a potential for greater protein degradation and(or) turnover rates as suggested by smaller muscle weights.
authors.affiliation: Department of Animal Science, University of California, Davis 95616-8521, USA.
authors.forename: A K
authors.initials: AK
authors.lastname: Sharma
authors.forename: Y B
authors.initials: YB
authors.lastname: Lee
authors.forename: J D
authors.initials: JD
authors.lastname: Murray
mesh_terms: D000318:Adrenergic beta-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000375:Aging / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000502:physiology; D002403:Cathepsins / Q000008:administration & dosage / Q000494:pharmacology; D002976:Clenbuterol / Q000008:administration & dosage / Q000494:pharmacology; D004247:DNA / Q000032:analysis; D005260:Female; D005838:Genotype; D013006:Growth Hormone / Q000235:genetics; D008297:Male; D008668:Metallothionein / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D008808:Mice, Inbred CBA / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D008822:Mice, Transgenic / Q000235:genetics / Q000254:growth & development* / Q000502:physiology; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000254:growth & development / Q000502:physiology; D009929:Organ Size; D012313:RNA / Q000032:analysis; D011897:Random Allocation; D012756:Sheep
chemical_list: D000318:Adrenergic beta-Agonists; D012313:RNA; D013006:Growth Hormone; D004247:DNA; D008668:Metallothionein; D002403:Cathepsins; D002976:Clenbuterol