A mass budget for transgenic "Supermice" engineered with extra rat growth hormone genes: evidence for energetic limitation

Abstract

Genetically engineered "Supermice" (Mus musculus, transgenic strain Tg[MT-1,rGH],Bri2) possess multiple copies of rat growth hormone genes yielding growth rates 220% that of normal mice. To discover how Supermice alter their acquisition and allocation of resources under elevated costs of growth, a resource allocation study was conducted on forty 50-day-old normal and transgenic male mice. Individual dry mass budgets were used to compare rates of growth, consumption, faecal deposition, digestive assimilation, and respiration over 11-day intervals. The mean body mass of transgenic mice was 153% that of normal animals during this period. Surprisingly, on a mass-specific basis, Supermice consumed 6% less food despite their higher investment in growth (normal: 0.50 ± 0.01 mg food/mg dry body mass per day; Supermice: 0.47 ± 0.01 mg food/mg dry body mass per day). Assimilation efficiency was also slightly lower in Supermice (64.1%) than in normal animals (66.7%). Enhanced growth was achieved entirely through improved conversion efficiencies. Gross and net production efficiencies of Supermice were 227 and 244% those of controls, respectively. Such increased efficiencies appeared to be the result of diverting resources from processes such as behaviour, longevity assurance, and other respiratory demands. Evidence for such trade-offs supports the "principle of allocation," a key assumption for theories of life-history evolution.

Oxidative stress in hypopituitary dwarf mice and in transgenic mice overexpressing human and bovine GH

“…We observed higher concentrations of these products than in normal mice. The life span of the transgenic mice in the study was also reduced to half that of normal animals (Kajiura and Rollo, 1994). Although it is uncertain how extra GH may increase oxidative stress, high levels appear to reduce the influence of insulin on glucose uptake in adipose tissue at a site down stream from the insulin receptor.…”

Adaptive Intrinsic Growth Rates: An Integration Across Taxa

“…In addition, rapid growth requires increased reading of DNA which increases damage to DNA; accumulation of error in DNA has been implicated in the senescence of animals (Hart and Setlow 1974). Strains of rodents selected for rapid growth have shorter lifespans and greater tumor production than control strains, lending support to these ideas (Eklund and Bradford 1977;Kajiura and Rollo 1994). Bradford and Famula (1984) noted that the same strains have an unusual susceptibility to external parasites suggesting that they also have poorly developed immune systems (see below).…”

“…"Supermice" contain multiple copies of rat growth hormone genes and grow twice as fast as untransformed mice. But because this increased growth rate is achieved with a slightly lower mass-specific feeding rate (Kajiura and Rollo 1994), tradeoffs should be apparent. Supermice make up for the energetic cost of rapid growth by spending significantly more time asleep and are less active when awake than wildtype siblings (Lachmansingh and Rollo 1994).…”

Evolution of growth rates under the constraint of growth‐development trade‐off in a fish

“…Such a large genetic variation in growth rates implies that trade-offs with fast growth are present (Arendt 1997;Angilletta et al 2003). Trade-offs between growth and reproduction (e.g., Reznick 1982;Anthony et al 1991), maintenance/repair (e.g., Hawkins 1991;Kajiura and Rollo 1994), defense (e.g., Smoker 1986;Arendt et al 2001), and behavior (e.g., Wieser et al 1988;Billerbeck et al 2001) have been demonstrated in a variety of taxa.…”