C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/J

Mice homozygous for the targeted mutation, commonly referred to as B1RB2R -/-, are viable, fertile and display no major defects. At 4 months of age non-manipulated B1RB2R -/- mice exhibit no significant differences in blood pressure or kidney function when compared to Bdkrb2 deficient mice (Stock No. 006860). Fasted B1RB2R -/- mice exhibit significantly lower levels of plasma nitrite/nitrate compared to Bdkrb2 deficient mice. Post-ischemic B1RB2R -/- mice exhibit significantly higher plasma levels of urea nitrogen and creatinine, higher levels of oxidative nuclear and mitochondrial DNA modification, and increased rates of apoptosis and mortality than either wildtype or Bdkrb2 deficient mice. Histological evaluation of the kidney indicates that post ischemic B1RB2R -/- mice exhibit more severe histological changes in the renal proximal tubules than either wildtype or Bdkrb2 deficient mice (Kakoki, et al, 2007). This Bdkrb1/Bdkrb2 targeted mutation is useful for studying the kallikrein-kinin system, specifically the role of bradykinin B1 receptor and bradykinin B2 receptor in oxidative stress, mitochondrial DNA damage, apoptosis, morphological and functional kidney changes, and other senescence-associated phenotypes. Mice homozygous for the targeted mutation and heterozygous for the Ins2Akita spontaneous mutation are viable and fertile. Similar to mice only heterozygous for the Ins2 mutation, the double mutant mice are severely diabetic: their body weights are 70% of wildtype, they consume over 3-fold the normal amount of food, and their urinary output is approximately 20-fold more than that of wildtype mice. Double mutant mice have markedly enlarged kidneys. Urinary albumin excretion in double mutants is almost 4-fold that of either single mutant, and double mutants experience more severe nephropathy than mice that are heterozygous for the Akita mutation alone. Megsin and nephrin expression is markedly increased in double mutant mice when compared to wildtype or to mice with either single mutation alone. By 12 months of age, double mutant mice experience hair loss due to a reduction in hair follicle numbers and thinning of the dermis. Double mutants have essentially no subcutaneous fat, severe kyphosis, reduced bone density, osteoporosis, testicular atrophy, lipofuscin accumulation in the renal proximal tubule and testicular Leydig cells, increased apoptosis in the testicular seminiferous tubules and intestinal villi, and a significantly reduced lifespan.


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Data (.csv filetype)

plasma glucose (mg/dL)

SeriesSexNAvgSD
C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/JBoth120490.78167.06
 Female55373.47152.22
 Male65590.05102.09
Avg = 551.82
Std = 145.78
N = 17
Age = 26 Avg = 509.65
Std = 176.42
N = 17
Age = 24 Avg = 497.33
Std = 162.43
N = 18
Age = 20 Avg = 452.44
Std = 159.48
N = 18
Age = 16 Avg = 448.94
Std = 163.07
N = 18
Age = 12 Avg = 512.67
Std = 184.93
N = 18
Age = 8 Avg = 460.29
Std = 141.96
N = 14
Age = 4 Avg = 551.82
Std = 145.78
N = 17
Age = 26 Avg = 509.65
Std = 176.42
N = 17
Age = 24 Avg = 497.33
Std = 162.43
N = 18
Age = 20 Avg = 452.44
Std = 159.48
N = 18
Age = 16 Avg = 448.94
Std = 163.07
N = 18
Age = 12 Avg = 512.67
Std = 184.93
N = 18
Age = 8 Avg = 460.29
Std = 141.96
N = 14
Age = 4

insulin, plasma (pg/ml)

SeriesSexNAvgSD
C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/JBoth54466.24554.42
 Female24730.42723.43
 Male30254.90184.66
Avg = 413.72
Std = 570.65
N = 18
Age = 24 Avg = 500.44
Std = 362.26
N = 18
Age = 16 Avg = 484.56
Std = 678.97
N = 18
Age = 8 Avg = 413.72
Std = 570.65
N = 18
Age = 24 Avg = 500.44
Std = 362.26
N = 18
Age = 16 Avg = 484.56
Std = 678.97
N = 18
Age = 8

W rodent (g)

SeriesSexNAvgSD
C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/JBoth21221.992.53
 Female9321.533.09
 Male11922.351.92
Avg = 21.92
Std = 2
N = 17
Age = 26 Avg = 23.85
Std = 2.26
N = 17
Age = 24 Avg = 23.52
Std = 2.13
N = 17
Age = 22 Avg = 23.51
Std = 2.14
N = 18
Age = 20 Avg = 22.63
Std = 1.73
N = 15
Age = 18 Avg = 22.89
Std = 1.7
N = 18
Age = 16 Avg = 22.63
Std = 1.29
N = 18
Age = 14 Avg = 22.51
Std = 1.76
N = 28
Age = 12 Avg = 21.72
Std = 1.71
N = 18
Age = 10 Avg = 20.54
Std = 1.81
N = 18
Age = 8 Avg = 19.13
Std = 1.69
N = 14
Age = 6 Avg = 17.34
Std = 1.85
N = 14
Age = 4 Avg = 21.92
Std = 2
N = 17
Age = 26 Avg = 23.85
Std = 2.26
N = 17
Age = 24 Avg = 23.52
Std = 2.13
N = 17
Age = 22 Avg = 23.51
Std = 2.14
N = 18
Age = 20 Avg = 22.63
Std = 1.73
N = 15
Age = 18 Avg = 22.89
Std = 1.7
N = 18
Age = 16 Avg = 22.63
Std = 1.29
N = 18
Age = 14 Avg = 22.51
Std = 1.76
N = 28
Age = 12 Avg = 21.72
Std = 1.71
N = 18
Age = 10 Avg = 20.54
Std = 1.81
N = 18
Age = 8 Avg = 19.13
Std = 1.69
N = 14
Age = 6 Avg = 17.34
Std = 1.85
N = 14
Age = 4

fat body mass (g)

SeriesSexNAvgSD
C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/JBoth173.860.83
 Female84.500.79
 Male93.300.23
Avg = 3.86
Std = 0.83
N = 17

lean body mass (g)

SeriesSexNAvgSD
C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/JBoth1718.461.62
 Female818.341.50
 Male918.581.71
Avg = 18.46
Std = 1.62
N = 17

%BF (rodent) (%)

SeriesSexNAvgSD
C57BL/6-Ins2Akita Bdkrb1/Bdkrb2tm2Mki/JBoth1717.232.73
 Female819.571.95
 Male915.161.23
Avg = 17.23
Std = 2.73
N = 17