Phenotype Information for KK.Cg-Ay/J (002468)

JAX® Mice Strain - KK.Cg-Ay/J

Stock Number 002468

The agouti yellow mutation in KK.Cg-Ay/J mice causes type 2 diabetes and moderate obesity.  Like the db and ob strains, both Ay/a sexes (yellow fur) are diabetic, but unlike those monogenic models wildtype a/a mice (black fur) are also partly affected because of the permissive KK/J genetic background.

Key phenotypes include:

  • Obesity in males and females (Figure 1) that is less severe than ob and db strains
  • Hyperglycemia by 6 weeks in males and 10 weeks in females (Figure 2, Table 1)
  • Glucose intolerance in males and females by 8 weeks (Figure 3)
  • Elevated serum glucose, HbA1c, lipids, insulin, and leptin (Figure 4).  Triglycerides in Ay/a are 3-4 times greater than BKS-db/db mice.

Figure 1 A Body weight growth curve and DEXA analysis. Left figure: 25-35 male and female Ay/a (yellow fur) and a/a (black fur) mice were fed LabDiet 5K52 formulation (6% fat w/w) between the ages of 4 and 16 weeks and were weighed weekly. Values show mean and one standard deviation. Right figure: Mice were weighed and then imaged with a Lunar PIXImus DEXA scanner. Calculations exclude the head. Values represent mean and one standard deviation of 4-5 non-fasted mice per group. Results were analyzed using a 2-way ANOVA with Sidak multiple comparisons test (GraphPad Prism 9.1). Significant differences between sexes (Ay/a genotype) and within sex (Ay/a vs a/a) are shown. * P < 0.05; ** P < 0.01; *** P < 0.001.

Figure 2 Non-fasted blood glucose. Weekly submental blood glucose measurements collected with a validated OneTouch Ultra 2 hand-held glucometer. Values represent mean and one standard deviation from the same mice weighed in Figure 1.

 

Table 1. Distribution of glucose values. The glucose values from Figure 2 are grouped to indicate the percentage of mice in each range.

 

Glucose range
(mg/dL)

Age (weeks)

4

6

8

10

12

14

16

Ay/a Females

Below 250

88%

52%

36%

29%

27%

18%

0%

250 - 349

12%

44%

55%

36%

9%

9%

100%

350 - 449

0%

0%

9%

29%

55%

36%

0%

Above 450

0%

4%

0%

7%

9%

36%

0%

Ay/a Males

Below 250

63%

4%

0%

25%

33%

9%

0%

250 - 349

31%

30%

25%

33%

17%

36%

0%

350 - 449

3%

41%

13%

0%

33%

27%

20%

Above 450

3%

26%

63%

42%

17%

27%

80%

 

Figure 3 Glucose tolerance test. After a 16 hour fast, serum was collected from Ay/a submental blood for an initial glucose reading (“Before”) and mice were then administered glucose by IP injection at 2g/kg body weight. Serum glucose was measured after 120 minutes (“After”). Values represent mean and one standard deviation of 4-5 mice per group. No significant differences between males and females were found in Before or After values when each age was analyzed separately by 2-way repeated measures ANOVA with Sidak multiple comparisons test (GraphPad Prism 9.1).

Figure 4 Serum chemistry and hormones. All values were measured from serum collected from submental blood except HbA1c, which was measured from submental whole blood. Values represent mean and one standard deviation of the same 9-10 non-fasted mice per age and sex, studied longitudinally. Results were obtained using a Beckman Coulter DxC 700 AU chemistry analyzer or Meso Scale SQ120 analyzer (insulin & leptin). Results were analyzed separately by parameter using a repeated measures mixed-effects model with Sidak’s multiple comparisons test (GraphPad Prism 9.1). Significant differences between sexes (Ay/a genotype) and within sex (Ay/a vs a/a) are shown. * P < 0.05, ** P < 0.01, *** P < 0.001; **** P < 0.0001.