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Severe Thermoregulatory Deficiencies in Mice with a Gene Deletion in Titin
Başlık:
Severe Thermoregulatory Deficiencies in Mice with a Gene Deletion in Titin
Yazar:
Miyano, Carissa, author.
ISBN:
9780438015333
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (44 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Kiisa C. Nishikawa Committee members: C. Loren Buck; Tinna Traustadóttir.
Özet:
Muscular dystrophy with myositis (mdm) mice, which carry a deletion in the muscle protein titin, shiver at a lower than expected frequency for their body size, have body temperatures that decrease below ambient temperatures of 34°C, and have reduced active muscle stiffness in vivo compared to their wild type siblings. The impairment in shivering thermogenesis could be due to the N2A deletion in the titin protein leading to more compliant muscles and lower shivering frequency. I hypothesized that the ability of mdm mice to use the other heat production mechanism, nonshivering thermogenesis (NST), may also be impaired and contribute to their hypothermic state. To assess the response to cold exposure, body temperature and metabolic rate were measured in wild type and mdm mice using open-flow respirometry at four ambient temperature ranges: 19--21°C, 23--25°C, 27--30°C, and 33--35°C. Following the temperature experiment, NST was maximally stimulated by administering 1.2 mg kg-1 of norepinephrine subcutaneously. In the temperature experiment, there was a significant interaction between genotype and temperature, with mdm mice having significantly higher metabolic rates at 27--30°C and lower metabolic rates at 23--25°C compared to wild type mice. After correcting metabolic rate for Q10 effects, mdm mice had lower metabolic rates compared to size-matched Perognathus longimembris (little pocket mouse). In addition, the capacity for NST estimated by area underneath the metabolic response curve was also reduced in mdm mice compared to wild type littermates. When comparing mdm mice to other mice with similar body mass (7g), the effects of low metabolic rate and capacity for NST were exacerbated because predicted values of metabolic rate and capacity for NST are larger for smaller animals. These results indicate that a deletion in N2A titin causes severe thermoregulatory defects at every level of thermoregulation, including NST. Direct effects of the titin mutation likely lead to the lower shivering frequency observed. Indirect effects likely lead to a lower capacity for NST and metabolism in general. Future studies should investigate effects on oxidative phosphorylation or other signaling pathways.
Notlar:
School code: 0391
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(693006.1) | 693006-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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