Mouse Genome Informatics
cn1
    Arxtm1Gldn/Arxtm1Gldn
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0

involves: 129 * Black Swiss * C57BL/6 * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• beta cell do not transdifferentiate into alpha cells unlike in Nkx2-2tm2.1Suss homozygotes (J:177838)

homeostasis/metabolism
(J:177838)


Mouse Genome Informatics
cn2
    Gjd2tm4Kwi/Gjd2tm4Kwi
Tg(Ins2-cre)23Herr/?

involves: 129P2/OlaHsd * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• Cx36 channels are non functional as determined by "tracer" studies (beta cells are uncoupled)
• increased basal secretion of insulin

homeostasis/metabolism
N
• normal in vivo tolerance for acute glucose load (J:174834)
• normal responsiveness to high glucose levels (16mM) (J:174834)
• increased basal secretion of insulin
• do not respond to physiological concentrations of glucose


Mouse Genome Informatics
cn3
    Cebpbtm1.1Maka/Cebpbtm1.1Maka
Ins2Akita/Ins2Akita
Tg(Ins2-cre)23Herr/0

involves: 129P2/OlaHsd * C57BL/6J * C57BL/6NSlc * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Abnormal glucose and insulin homeostasis in Ins2Akita/Ins2Akita and Ins2Akita/Ins2Akita Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 but not Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 mice.

endocrine/exocrine glands
• expression of apoptosis markers in the pancreas islet is decreased compared to in Ins2Akita homozygotes
• mice exhibit improved beta cell mass compared to in Ins2Akita homozygotes
• pancreatic insulin levels are decreased compared to in wild-type mice
• however, pancreatic insulin content is 8-fold higher than in Ins2Akita homozygotes

homeostasis/metabolism
• pancreatic insulin levels are decreased compared to in wild-type mice
• however, pancreatic insulin content is 8-fold higher than in Ins2Akita homozygotes
• mice exhibit increased circulating glucose levels compared to in wild-type mice
• however, glucose serum level are increased compared to in Ins2Akita homozygotes
• mice exhibit decreased circulating glucose levels compared to in wild-type mice
• however, insulin serum level are increased compared to in Ins2Akita homozygotes

cellular
• expression of apoptosis markers in the pancreas islet is decreased compared to in Ins2Akita homozygotes


Mouse Genome Informatics
cn4
    Cebpbtm1.1Maka/Cebpbtm1.1Maka
Leprdb/Leprdb
Tg(Ins2-cre)23Herr/0

involves: 129P2/OlaHsd * C57BL/6J * C57BLKS/J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Increased beta cell mass in Leprdb/Leprdb mice and Leprdb/Leprdb Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands
• pancreatic islet cell apoptosis is decreased compared to in Leprdb homozygotes
• compared to in Leprdb homozygotes

homeostasis/metabolism
• hyperglycemia develops more slowly and is ameliorated compared to in Leprdb homozygotes
• at 12 weeks, plasma insulin levels are increased compared to in Leprdb homozygotes and wild-type mice

cellular
• pancreatic islet cell apoptosis is decreased compared to in Leprdb homozygotes


Mouse Genome Informatics
cn5
    Men1tm1.2Zqw/Men1tm1.2Zqw
Tg(Ins2-cre)23Herr/0

involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 41.5% of mice developed insulinomas by 6 months of age and by 10 months, 100% of mutants have advanced insulinomas (carcinomas)

endocrine/exocrine glands
• hyperplastic islets as early as 2 months of age, which progresses with aging

homeostasis/metabolism
• glucose levels decreased after 8 months of agae, as tumorigenesis progressed
• insulin levels increased starting at 4 months of age and continued to increase with age

Mouse Models of Human Disease
OMIM IDRef(s)
Multiple Endocrine Neoplasia, Type I; MEN1 131100 J:85133


Mouse Genome Informatics
cn6
    Cebpbtm1.1Maka/Cebpbtm1.1Maka
Tg(Ins2-cre)23Herr/0

involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Higher plasma insulin levels and increased pancreatic insulin content in Cebpbtm1.1Maka/Cebpbtm1.1Maka Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands
• pancreas insulin levels are higher than in Cebpbtm1.1Maka homozygotes

homeostasis/metabolism
N
• mice exhibit normal circulating insulin and glucose levels (J:156725)
• pancreas insulin levels are higher than in Cebpbtm1.1Maka homozygotes


Mouse Genome Informatics
cn7
    Dnmt3atm1Jae/Dnmt3atm1Jae
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0

involves: 129S/Sv * Black Swiss * C57BL/6 * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mice exhibit beta to alpha cell transdifferentiation

cellular
• mice exhibit beta to alpha cell transdifferentiation


Mouse Genome Informatics
cn8
    Glud1tm1.1Pma/Glud1tm1.1Pma
Tg(Ins2-cre)23Herr/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Glud1tm1.1Pma/Glud1tm1.1Pma Tg(Ins2-cre)23Herr/0 mice have impaired insulin secretion

endocrine/exocrine glands
• 67% of islets are disorganized compared to 30% in wild-type mice
• however, pancreas insulin content is normal
• glucose-stimulated insulin secretion in the pancreas is decreased 48% during the first phase and 37% in the second phase compared to in similarly treated wild-type mice
• isolated islets exhibit a 68% reduction in the first phase and 49% reduction in the second phase of glucose-stimulated insulin secretion compared to similarly treated wild-type islets
• insulin secretion is decreased 38% 15 minutes following intraperitoneal glucose injection at 2 months of age
• however, fasted insulin levels are normal and ectopic expression of Glud1 in islet cells restores normal glucose-stimulated insulin secretion

growth/size
N
• despite disruptions in stimulated insulin secretion, mice exhibit normal growth (J:145558)

homeostasis/metabolism
N
• despite disruptions in stimulated insulin secretion, mice exhibit normal glucose homeostasis and age-dependent insulin resistance (J:145558)
• glucose-stimulated insulin secretion in the pancreas is decreased 48% during the first phase and 37% in the second phase compared to in similarly treated wild-type mice
• isolated islets exhibit a 68% reduction in the first phase and 49% reduction in the second phase of glucose-stimulated insulin secretion compared to similarly treated wild-type islets
• insulin secretion is decreased 38% 15 minutes following intraperitoneal glucose injection at 2 months of age
• however, fasted insulin levels are normal and ectopic expression of Glud1 in islet cells restores normal glucose-stimulated insulin secretion
• 55% when in a fed state
• glutamate dehydrogenase activity is reduced by 60% in islets compared to in wild-type mice


Mouse Genome Informatics
cn9
    Gsk3btm2Jrw/Gsk3btm2Jrw
Irs2tm1Mfw/Irs2tm1Mfw
Tg(Ins2-cre)23Herr/?

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• fed blood glucose concentration were significantly reduced relative to that in Irs2tm1Mfw homozygous mice, though remained slightly higher than normal control
• both fasting and fed insulin levels were higher than in wild-type mice similar to the level found in Irs2tm1Mfw homozygous mice


Mouse Genome Informatics
cn10
    Cdh1tm2Kem/Cdh1tm2Kem
Tg(Ins2-cre)23Herr/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• in 7 day and 1, but not 3, month old mice
• 2-fold increase in blood vessel density in insulin-positive areas
• however, beta cell organization is normal
• at 3 months
• 2.5-fold at 3 to 4 months
• glucose-stimulated at 4, but not 1, months

homeostasis/metabolism
• glucose-stimulated at 4, but not 1, months
• at 3 to 4 months

cardiovascular system
• 2-fold increase in blood vessel density in insulin-positive areas

growth/size
N
• mice exhibit normal body weight (J:196410)

cellular
• in 7 day and 1, but not 3, month old mice


Mouse Genome Informatics
cn11
    Gt(ROSA)26Sortm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0

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

Reduction in islet insulin content in Gt(ROSA)26Sortm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor+ Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands
• the percentage of islet area occupied by beta cells is somewhat decreased
• alpha cells are not confined to the islet mantle
• relative increase in the number of alpha cells
• some of the beta cells are irregularly shaped
• the percentage of beta cells is decreased
• reduction in islet insulin content by 5 weeks of age but not at 5 days of age
• K(sub)ATP currents in beta cells are larger compared to control cells an inhibition of these currents by glucose is impaired
• glucose induced calcium responses of beta cells are impaired
• impairment in basal and both first and second-phase glucose induced insulin secretion

homeostasis/metabolism
• impairment in basal and both first and second-phase glucose induced insulin secretion
• elevated glucose levels develop by P3
• overt diabetes develops by 5 weeks of age

growth/size
• seen in males by 4 to 6 weeks of age

renal/urinary system
• produce copious amounts of urine after when a few weeks old

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Permanent Neonatal; PNDM 606176 J:144715


Mouse Genome Informatics
cn12
    Tg(Ins2-cre)23Herr/0
Tsc2tm1Kido/Tsc2tm1Kido

involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• in a fed state from 4 until 32 weeks of age
• after 36 week of age, mice exhibit increased plasma glucose levels compared to wild-type mice
• however, treatment of mice with rapamycin prevents the development of hyperglycemia
• after 40 weeks of age
• however, treatment of mice with rapamycin prevents the decrease in plasma insulin levels
• at 12 weeks of age until 32 weeks
• at 8 weeks of age
• at 8 weeks of age

endocrine/exocrine glands
• at 40 weeks of age, islet cell density is decreased compared to in wild-type mice
• at 6 weeks of age, beta cell mass and size is increased compared to in wild-type mice
• at 40 weeks of age, beta cell mass decreases to lower than normal
• however, the number of beta cells is normal
• beta cell size is not decreased after 40 weeks of age
• at 40 weeks of age, beta cell number is decreased due to apoptosis
• however, treatment of mice with rapamycin prevents the decrease in beta cell mass observed at 40 weeks of age
• at 6 weeks of age

growth/size
• after 48 weeks of age


Mouse Genome Informatics
cn13
    Pdpk1tm1Maka/Pdpk1tm1Maka
Tg(Ins2-cre)23Herr/0

involves: 129S4/SvJae * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all male knockouts die between 12 and 24 weeks of age from uncontrolled diabetes

growth/size
• after 8 weeks of age, mutant body weights increase at a lower rate compared to control

homeostasis/metabolism
• mutants exhibit hyperglycemia with blood glucose levels greater than 500 mg/dl by 12-16 weeks of age
• at 12 weeks of age, plasma insulin in the fed state is lower in mutants; by 20 weeks of age, it is close to the lower detection limit

endocrine/exocrine glands
• beta cells proliferate much less in islets of null mice; proliferation is ~50% lower at 4 weeks and ~75% lower at 8 weeks
• at 4 weeks of age, size of islets is smaller than in controls; islet density is lower than in controls and is only ~40% that of controls at 16 weeks
• insulin content of the pancreas in null mice is lower than in control mice


Mouse Genome Informatics
cn14
    Foxo1tm1Whb/Foxo1+
Pdpk1tm1Maka/Pdpk1tm1Maka
Tg(Ins2-cre)23Herr/0

involves: 129S4/SvJae * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• double mutants have improved blood glucose levels compared to Pdk1-deficient mice; glucose levels of 200-300 mg/dl are maintained in double mutants at 20-24 weeks
• plasma insulin level is significantly higher in double mutants compared to Pdk1-deficient mice

endocrine/exocrine glands
• Foxo-haploinsufficiency results in a significant increase in beta cell number in double mutants
• insulin content of the pancreas in double mutant mice is 6-fold higher than in Pdk1-deficient mice; number of proliferating beta cells is much greater in double mutants compared to Pdk1-null mice

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:109224


Mouse Genome Informatics
cn15
    Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0

involves: 129S6/SvEvTac * Black Swiss * C57BL/6 * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• beta cells are reprogrammed to alpha cells

cellular
• beta cells are reprogrammed to alpha cells


Mouse Genome Informatics
cn16
    Men1tm2.1Mmey/Men1tm2.1Mmey
Tg(Ins2-cre)23Herr/0

involves: 129S6/SvEvTac * C57BL/6 * CBA/J * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival is 45 weeks

endocrine/exocrine glands
• in 5 of 10 mice at 2 months of age
• in 4 of 9 mice at 4 months of age
• in 5 of 10 mice at 2 months of age
• in 4 of 9 mice at 4 months of age
• islet proliferation is increased compared to in control mice

tumorigenesis
• in 3 of 16 mice at 8 months of age
• in all mice at 10 months of age


Mouse Genome Informatics
cn17
    Kdm5atm1Kael/Kdm5atm1Kael
Men1tm2.1Mmey/Men1tm2.1Mmey
Tg(Ins2-cre)23Herr/0

involves: 129S6/SvEvTac * C57BL/6 * CBA/J * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival is 69 weeks

endocrine/exocrine glands
N
• islet proliferation is normal (J:175625)
• atypia in 2 of 16 mice at 8 months of age
• in 1 of 8 mice at 2 months of age
• in 3 of 16 mice at 8 months of age

tumorigenesis
• in 2 of 21 mice at 10 months of age


Mouse Genome Informatics
cn18
    Wfs1tm1Perm/Wfs1tm1Perm
Tg(Ins2-cre)23Herr/0

involves: 129X1/SvJ * C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• at 24 weeks of age, but not at 16, have lower weights

homeostasis/metabolism
• both fasting and fed glucose:insulin ratios are elevated
• develop diabetes
• impaired glucose-stimulated insulin secretion
• progressive development of hyperglycemia
• fed glucose concentrations are higher at 24 weeks of age, but mean fasted glucose concentrations are normal
• fasting insulin levels are significantly reduced at 12 weeks of age and fed insulin levels are reduced at 12 and 24 weeks of age
• progressive glucose intolerance, with mild glucose intolerance 60 min after glucose injection by 12 weeks of age and significant glucose intolerance 30, 60, and 120 min after glucose injection by 16 weeks of age

endocrine/exocrine glands
• 2.5-fold increase in caspase 3-positive nuclei in islets, indicating increased apoptosis
• reduction of beta cell mass is seen at 24 weeks of age
• reduction of the beta cell:pancreas ratio is seen at 24 weeks of age
• asymmetry and disruption of islet architecture is apparent at 12 weeks of age, with an alteration of the ratio of beta to non-beta cells within the islet
• secretory granules are reduced in beta cells and majority of cells exhibit abundant dilated ER, indicating increased ER stress in beta cells
• impaired glucose-stimulated insulin secretion

Mouse Models of Human Disease
OMIM IDRef(s)
Wolfram Syndrome 1; WFS1 222300 J:104712


Mouse Genome Informatics
cn19
    Dnmt3atm1Jae/Dnmt3atm1Jae
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0

involves: Black Swiss * C57BL/6 * CBA/J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands


Mouse Genome Informatics
cn20
    Gt(ROSA)26Sortm1(CAG-Kcnj11*,-GFP)Nich/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0

involves: C57BL/6 * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• body weight of neonates is normal
• growth retardation after birth
• body weight is 50% of controls by three months
• pancreas weight/body weight ratio is normal

homeostasis/metabolism
• by 6 weeks of age loss of response to injected glucose
• dramatic lowering of glucose levels after insulin injection
• blood glucose is over 200mg/dl within 2 weeks of birth
• progressively increases to over 600mg/dl by 2 months
• levels become undetectable as diabetes becomes more severe
• significantly elevated early in diabetes development
• plasma insulin levels decrease with time

endocrine/exocrine glands
• alpha cells infiltrate center of islets after the onset of diabetes
• are lost as diabetes becomes more severe
• beta cells are lost as diabetes develops
• number of islet is reduced by 50% early in diabetes and by more than 90% later
• islet mass decreases to about 10% of controls
• pancreas weight relative to controls becomes reduced over time
• pancreas weight/body weight ratio is normal
• insulin content of pancreas drops to about 10% of control levels
• by 6 weeks of age loss of response to injected glucose

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Permanent Neonatal; PNDM 606176 J:146650


Mouse Genome Informatics
cn21
    Huwe1tm1Wgu/Y
Tg(Ins2-cre)23Herr/0

involves: C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Loss of pancreatic beta-cells in aged Huwe1tm1Wgu/Y Tg(Ins2-cre)23Herr/0 mice

mortality/aging
• more than half mice died at less than 1 year of age due to severe diabetic symptoms (J:182446)

homeostasis/metabolism
• in fasting and fed mice at 6 and 9 months of age (J:182446)
• progressive (J:182446)
• in fed mice at 6 and 9 months (J:182446)
• in fasting mice at 9 months (J:182446)
• at 3 and 6 months (J:182446)

endocrine/exocrine glands
• at 6 months and worsening at 9 months (J:182446)
• at 6 months and worsening at 9 months, mice exhibit infiltration of alpha cells into the middle of islets unlike in wild-type mice (J:182446)

renal/urinary system
• enlarged bladder (J:182446)
(J:182446)

growth/size
• at 9 months (J:182446)


Mouse Genome Informatics
cn22
    Huwe1tm1Wgu/Y
Tg(Ins2-cre)23Herr/0
Trp53tm1Thl/Trp53tm1Thl

involves: C57BL/6J * CBA/J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice survive longer than Huwe1tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)

homeostasis/metabolism
N
• diabetic symptoms (serum glucose and insulin levels and glucose intolerance) observed in Huwe1tm1Wgu/Y Tg(Ins2-cre)23Herr mice are improved (J:182446)
• in fasting mice at 9 months but not as severe as in Huwe1tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)
• in fed mice at 3, 6 and 9 months but not as severe as in Huwe1tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)

endocrine/exocrine glands
N
• islet organization is improved compared to in Huwe1tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)