The streptozotocin-induced diabetic nude mouse model: differences between animals from different sources - PubMed (original) (raw)

Comparative Study

The streptozotocin-induced diabetic nude mouse model: differences between animals from different sources

Melanie L Graham et al. Comp Med. 2011 Aug.

Abstract

Diabetes is induced in mice by using streptozotocin (STZ), a compound that has a preferential toxicity toward pancreatic β cells. We evaluated nude male mice from various sources for their sensitivity to a single high dose (160 to 240 mg/kg) of STZ. Diabetes was induced in male mice (age: median, 12 wk; interquartile range, 11 to 14 wk; body weight, about 30 g) from Taconic Farms (TAC), Jackson Laboratories (JAX), and Charles River Laboratories (CRL). Mice were monitored for 30 d for adverse side effects, blood glucose, and insulin requirements. In CRL mice given 240 mg/kg STZ, more than 95% developed diabetes within 4 to 5 d, and loss of body weight was relatively low (mean, 0.4 g). In comparison, both TAC and JAX mice were more sensitive to STZ, as evidenced by faster development of diabetes (even at a lower STZ dose), greater need for insulin after STZ, greater body weight loss (mean: TAC, 3.5 g; JAX, 3.7 g), and greater mortality. We recommend conducting exploratory safety assessments when selecting a nude mouse source, with the aim of limiting morbidity and mortality to less than 10%.

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Figures

Figure 1.

Figure 1.

(A) Diabetes induction and (B) survival after diabetes induction in male nude mice from Charles River Laboratories (CRL), Jackson Laboratories (JAX), and Taconic Farms (TAC). (A) The development of diabetes (glucose greater than or equal to 300 mg/dL) is presented as Kaplan–Meier estimates plotted over time after STZ infusion. 100% of JAX and TAC mice rapidly developed diabetes by day 2 after STZ injection, whereas CRL mice needed 5 d to achieve a diabetic state in 92% of mice (P < 0.001). (B) Death or euthanasia is presented as Kaplan–Meier estimates plotted over time after STZ infusion. CRL mice demonstrated significantly better survival (P < 0.001), compared with JAX and TAC mice.

Figure 2.

Figure 2.

Blood glucose values (top row) and body weight (bottom row) in response to insulin (glargine) treatment (U/kg daily) after diabetes induction by using STZ in male nude mice from Charles River Laboratories (CRL), Jackson Laboratories (JAX), and Taconic Farms (TAC). Data are presented as mean ± 1 SD. Dashed lines indicate average blood glucose value after STZ (top row) and average baseline weight (bottom row).

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