Mouse Genome Informatics
hm1
    Insrtm1Dac/Insrtm1Dac
involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 72 hours of birth

homeostasis/metabolism
• about 10% with diabetes
• plasma glucose levels rose sharply after birth; measured between 24-37 mmol/l
• plasma insulin levels rose sharply after birth to levels approximately 7 times that of controls
• homozygous mice developed diabetic ketoacidosis, with ketone bodies in urine; urinary acetoacetate measured between 8-16 mmol/l

liver/biliary system
• steatosis; fatty degeneration of liver

renal/urinary system
• homozygous mice developed diabetic ketoacidosis, with ketone bodies in urine; urinary acetoacetate measured between 8-16 mmol/l

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Donohue Syndrome 246200 J:33408


Mouse Genome Informatics
ht2
    Insrtm1Dac/Insr+
involves: 129 * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• both fasting and fed insulin levels were higher than in wild-type mice

endocrine/exocrine glands
• increased beta cell mass


Mouse Genome Informatics
ht3
    Insrtm1Dac/Insr+
involves: C3H/HeH * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• beta islet cells secrete about twice as much insulin as controls in the absence of extracellular glucose

homeostasis/metabolism
• beta islet cells secrete about twice as much insulin as controls in the absence of extracellular glucose
• circulating insulin levels are almost 3-fold higher and continue to remain higher than controls during a glucose challenge


Mouse Genome Informatics
cn4
    Actbtm1(INSR)Dac/Actbtm1(INSR)Dac
Insrtm1Dac/Insrtm1Dac
Tg(Hsp70-1-cre)6Arge/?

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 6 and 8 weeks

homeostasis/metabolism
• diabetic in one week
• extremely elevated


Mouse Genome Informatics
cn5
    Actbtm1(INSR)Dac/Actbtm1(INSR)Dac
Insrtm1Dac/Insrtm1Dac
Tg(Syn1-cre)671Jxm/?

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 6 and 8 weeks

homeostasis/metabolism
• diabetic in one week
• extremely elevated


Mouse Genome Informatics
cn6
    Actbtm1(INSR)Dac/Actbtm1(INSR)Dac
Insrtm1Dac/Insrtm1Dac
Tg(Nes-cre)1Kln/?

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 6 and 8 weeks

homeostasis/metabolism
• diabetic in one week
• extremely elevated


Mouse Genome Informatics
cn7
    Actbtm1(INSR)Dac/Actbtm1(INSR)Dac
Insrtm1Dac/Insrtm1Dac
Tg(Camk2a-cre)#Szi/?

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 6 and 8 weeks

homeostasis/metabolism
• diabetic in one week
• extremely elevated


Mouse Genome Informatics
cn8
    Insrtm1Khn/Insrtm1Dac
Tg(Ckmm-cre)5Khn/0

involves: 129S4/SvJae * C57BL/6J * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in the fed state, incomplete penetrance


Mouse Genome Informatics
cx9
    Gsk3btm1Jrw/Gsk3b+
Insrtm1Dac/Insr+

involves: 129 * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• decreased fasting glucose level relative to those in Insrtm1Dac heterozygous mice
• the rate of glucose disposal and glucose infusion were increased relative to those in Insrtm1Dac heterozygous mice
• hepatic glucose production is comparable to that in Insrtm1Dac heterozygous mice
• the serum insulin values were significantly decreased relative to those in Insrtm1Dac heterozygous mice in both the fasting and the fed state
• the values were significantly elevated relative to that in Gsk3btm1Jrw heterozygous mice
• compared to Insrtm1Dac heterozygous mice
• improved over Insrtm1Dac heterozygous mice, but still insulin resistant compared to wild-type

endocrine/exocrine glands
• reduced beta cell mass over Insrtm1Dac heterozygous mice


Mouse Genome Informatics
cx10
    Igf1rtm1Arge/Igf1rtm1Arge
Insrtm1Dac/Insrtm1Dac
Insrrtm1Dac/Insrrtm1Dac

involves: 129S/SvEv * 129S1/Sv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• XY mice at E17.5 showed gonad location and histology consistent with ovary development
• cause inferred as decrease in proliferation of Sry -expressing cells


Mouse Genome Informatics
cx11
    Igf1rtm1Arge/Igf1rtm1Arge
Insrtm1Dac/Insr+
Insrrtm1Dac/Insrrtm1Dac

involves: 129S/SvEv * 129S1/Sv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• XY mice may develop testes, ovotestes, and/or ovaries
• gonad type is suggested by degree of gonadal descent and histological analyses


Mouse Genome Informatics
cx12
    Igf1rtm1Arge/Igf1rtm1Arge
Insrtm1Dac/Insrtm1Dac

involves: 129S/SvEv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• determined by partial descent of gonads and histological analyses showing ovarian and testicular tissue
• partial male-to-female sex reversal is observed


Mouse Genome Informatics
cx13
    Actbtm1(INSR)Dac/Actbtm1(INSR)Dac
Insrtm1Dac/Insrtm1Dac

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die within a few days of birth

homeostasis/metabolism
• diabetic ketosis
• cause of early death


Mouse Genome Informatics
cx14
    Insrtm1Dac/Insr+
Irs2tm1Mfw/Irs2tm1Mfw

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

homeostasis/metabolism
• diabetic at 6 to 8 weeks of age

endocrine/exocrine glands
• undetectable at 8 weeks of age


Mouse Genome Informatics
cx15
    Insrtm1Dac/Insrtm1Dac
Insrrtm1Dac/Insrrtm1Dac

involves: 129S1/Sv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mice die within 5 days of birth

homeostasis/metabolism
• similar to Insr mutant mice; plasma glucose levels rose sharply after birth
• similar to Insr mutant mice; plasma insulin levels rose sharply after birth
• compound homozygous mice developed diabetic ketoacidosis, with ketone bodies in urine

renal/urinary system
• compound homozygous mice developed diabetic ketoacidosis, with ketone bodies in urine


Mouse Genome Informatics
cx16
    Foxo1tm1Whb/Foxo1+
Insrtm1Dac/Insrtm1Dac

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• due to diabetic ketoacidosis

homeostasis/metabolism
• 25% reduction in glucose levels relative to Insrtm1Dac homozygotes


Mouse Genome Informatics
cx17
    Foxo1tm1Whb/Foxo1+
Insrtm1Dac/Insr+

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• normal insulin and glucose levels at both 2 and 6 months (J:79560)
• no diabetes (J:79560)


Mouse Genome Informatics
cx18
    Foxo1tm2.1Dac/Foxo1tm2.1Dac
Insrtm1Dac/Insr+

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in fasted and re-fed mice
• slightly impaired hypoglycemic response in an insulin intolerance test


Mouse Genome Informatics
cx19
    Insrtm1Dac/Insrtm1Dac
Tg(TTR-INSR)L1Dac/0

involves: 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• weigh 80% of control mice
• limited recovery from low birth weight

homeostasis/metabolism
• glucose levels remain normal in 90% of mice at 2 months of age
• 35% are diabetic at 6 months
• life spans remain normal
• 10% increase in resting energy expenditure

endocrine/exocrine glands
• moderately decreased
• islets are otherwise normal

reproductive system
N
• normal fertility (J:91350)


Mouse Genome Informatics
cx20
    Insrtm1Dac/Insrtm1Dac
Tg(TTR-INSR)L2Dac/0

involves: 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 3 weeks and 8 months

growth/size/body
• remain growth retarded throughout life

adipose tissue
• lack white adipose tissue

liver/biliary system
• hepatomegaly
• fatty liver degeneration

homeostasis/metabolism
• diabetic at 2 months

endocrine/exocrine glands
• extensive loss of insulin positive cells at 4 months

reproductive system


Mouse Genome Informatics
cx21
    Insrtm1Dac/Insrtm1Dac
Tg(TTR-INSR)L3Dac/0

involves: 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 3 weeks and 8 months

growth/size/body
• weight is 60% of controls
• remain growth retarded throughout life

adipose tissue
• lack white adipose tissue

liver/biliary system
• hepatomegaly
• fatty liver degeneration

homeostasis/metabolism
• diabetic at 2 months
• by four weeks

endocrine/exocrine glands
• extensive loss of insulin positive cells at 4 months

reproductive system


Mouse Genome Informatics
cx22
    Insrtm1Dac/Insr+
Sox4Igt4/Sox4+

involves: C3H/HeH * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• these mice have impaired glucose tolerance with glucose levels significantly higher than controls 60 and 120 minutes after glucose administration
• the glucose levels are higher than in mice carrying the mutant Sox4 allele on a background that is homozygote for the wild-type allele of Insr