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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID
Tg(Ins2-cre)23Herr
transgene insertion 23, Pedro Luis Herrera
MGI:2387567
Summary 25 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
cn1
Arxtm1Gldn/Arxtm1Gldn
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0
involves: 129 * Black Swiss * C57BL/6 * CBA/J * SJL MGI:5297819
cn2
Gjd2tm4Kwi/Gjd2tm4Kwi
Tg(Ins2-cre)23Herr/?
involves: 129P2/OlaHsd * C57BL/6 * CBA MGI:5141707
cn3
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Ins2Akita/Ins2Akita
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * C57BL/6NSlc * CBA/J MGI:4421497
cn4
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Leprdb/Leprdb
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * C57BLKS/J * CBA/J MGI:4421499
cn5
Men1tm1.2Zqw/Men1tm1.2Zqw
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * CBA/J MGI:2675251
cn6
Ago2tm1.1Tara/Ago2tm1.1Tara
Lepob/Lepob
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * CBA/J MGI:5585185
cn7
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * CBA/J MGI:4421496
cn8
Ago2tm1.1Tara/Ago2tm1.1Tara
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6J * CBA/J MGI:5585184
cn9
Glud1tm1.1Pma/Glud1tm1.1Pma
Tg(Ins2-cre)23Herr/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA/J * SJL MGI:3835754
cn10
Gsk3btm2Jrw/Gsk3btm2Jrw
Irs2tm1Mfw/Irs2tm1Mfw
Tg(Ins2-cre)23Herr/?
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J MGI:3802546
cn11
Cdh1tm2Kem/Cdh1tm2Kem
Tg(Ins2-cre)23Herr/0
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J MGI:5494970
cn12
Gt(ROSA)26Sortm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0
involves: 129S4/SvJae * C57BL/6 MGI:3832577
cn13
Tg(Ins2-cre)23Herr/0
Tsc2tm1Kido/Tsc2tm1Kido
involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA/J MGI:3797790
cn14
Foxo1tm1Whb/Foxo1+
Pdpk1tm1Maka/Pdpk1tm1Maka
Tg(Ins2-cre)23Herr/0
involves: 129S4/SvJae * C57BL/6J * CBA/J MGI:3629034
cn15
Pdpk1tm1Maka/Pdpk1tm1Maka
Tg(Ins2-cre)23Herr/0
involves: 129S4/SvJae * C57BL/6J * CBA/J MGI:3629033
cn16
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 MGI:5297841
cn17
Foxo1tm1Rdp/Foxo1tm1Rdp
Foxo3tm1Rdp/Foxo3tm1Rdp
Foxo4tm1Rdp/Foxo4tm1Rdp
Tg(Ins2-cre)23Herr/0
involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * CBA/J MGI:5638417
cn18
Kdm5atm1Kael/Kdm5atm1Kael
Men1tm2.1Mmey/Men1tm2.1Mmey
Tg(Ins2-cre)23Herr/0
involves: 129S6/SvEvTac * C57BL/6 * CBA/J * FVB/N MGI:5296660
cn19
Men1tm2.1Mmey/Men1tm2.1Mmey
Tg(Ins2-cre)23Herr/0
involves: 129S6/SvEvTac * C57BL/6 * CBA/J * FVB/N MGI:5296659
cn20
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 MGI:5297821
cn21
Wfs1tm1Perm/Wfs1tm1Perm
Tg(Ins2-cre)23Herr/0
involves: 129X1/SvJ * C57BL/6J * CBA/J MGI:3614209
cn22
Dnmt3atm1Jae/Dnmt3atm1Jae
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0
involves: Black Swiss * C57BL/6 * CBA/J * SJL MGI:5297820
cn23
Gt(ROSA)26Sortm1(CAG-Kcnj11*,-GFP)Nich/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0
involves: C57BL/6 * CBA/J MGI:4430413
cn24
Huwe1tm1Wgu/Y
Tg(Ins2-cre)23Herr/0
Trp53tm1Thl/Trp53tm1Thl
involves: C57BL/6J * CBA/J MGI:5315853
cn25
Huwe1tm1Wgu/Y
Tg(Ins2-cre)23Herr/0
involves: C57BL/6J * CBA/J MGI:5315852


Genotype
MGI:5297819
cn1
Allelic
Composition
Arxtm1Gldn/Arxtm1Gldn
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129 * Black Swiss * C57BL/6 * CBA/J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Arxtm1Gldn mutation (0 available); any Arx mutation (19 available)
Nkx2-2tm2.1Suss mutation (0 available); any Nkx2-2 mutation (4 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
N
• beta cell do not transdifferentiate into alpha cells unlike in Nkx2-2tm2.1Suss homozygotes

homeostasis/metabolism




Genotype
MGI:5141707
cn2
Allelic
Composition
Gjd2tm4Kwi/Gjd2tm4Kwi
Tg(Ins2-cre)23Herr/?
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6 * CBA
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gjd2tm4Kwi mutation (1 available); any Gjd2 mutation (10 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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
• normal responsiveness to high glucose levels (16mM)
• increased basal secretion of insulin
• do not respond to physiological concentrations of glucose




Genotype
MGI:4421497
cn3
Allelic
Composition
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Ins2Akita/Ins2Akita
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * C57BL/6NSlc * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cebpbtm1.1Maka mutation (0 available); any Cebpb mutation (11 available)
Ins2Akita mutation (13 available); any Ins2 mutation (23 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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




Genotype
MGI:4421499
cn4
Allelic
Composition
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Leprdb/Leprdb
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * C57BLKS/J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cebpbtm1.1Maka mutation (0 available); any Cebpb mutation (11 available)
Leprdb mutation (11 available); any Lepr mutation (65 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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




Genotype
MGI:2675251
cn5
Allelic
Composition
Men1tm1.2Zqw/Men1tm1.2Zqw
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Men1tm1.2Zqw mutation (1 available); any Men1 mutation (22 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
neoplasm
• 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
• 41.5% of mice developed insulinomas by 6 months of age and by 10 months, 100% of mutants have advanced insulinomas (carcinomas)

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 ID Ref(s)
Multiple Endocrine Neoplasia, Type I; MEN1 131100 J:85133




Genotype
MGI:5585185
cn6
Allelic
Composition
Ago2tm1.1Tara/Ago2tm1.1Tara
Lepob/Lepob
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ago2tm1.1Tara mutation (1 available); any Ago2 mutation (31 available)
Lepob mutation (6 available); any Lep mutation (14 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• random glucose compared with Lepob homozygotes
• compared with Lepob homozygotes
• after glucose challenge
• after glucose challenge compared with Lepob homozygotes

endocrine/exocrine glands
N
• mice exhibit normal numbers of glucagon expressing cells and pancreatic mass
• not as severe as in Lepob homozygotes
• not as severe as in Lepob homozygotes




Genotype
MGI:4421496
cn7
Allelic
Composition
Cebpbtm1.1Maka/Cebpbtm1.1Maka
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cebpbtm1.1Maka mutation (0 available); any Cebpb mutation (11 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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
• pancreas insulin levels are higher than in Cebpbtm1.1Maka homozygotes




Genotype
MGI:5585184
cn8
Allelic
Composition
Ago2tm1.1Tara/Ago2tm1.1Tara
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129P2/OlaHsd * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ago2tm1.1Tara mutation (1 available); any Ago2 mutation (31 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
N
• mice exhibit normal islet architecture, alpha cell number, total pancreas mass and beta cell cell death
• mice fed a high fat diet exhibit normal islet morphometry
• increased beta cell size and total number of granules
• however, the number of docked granules is normal

homeostasis/metabolism
N
• mice fed a high fat diet exhibit normal glucose tolerance and energy expenditure
• at 10 weeks without altered insulin sensitivity

cellular




Genotype
MGI:3835754
cn9
Allelic
Composition
Glud1tm1.1Pma/Glud1tm1.1Pma
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * CBA/J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Glud1tm1.1Pma mutation (0 available); any Glud1 mutation (34 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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/body
N
• despite disruptions in stimulated insulin secretion, mice exhibit normal growth

homeostasis/metabolism
N
• despite disruptions in stimulated insulin secretion, mice exhibit normal glucose homeostasis and age-dependent insulin resistance
• 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




Genotype
MGI:3802546
cn10
Allelic
Composition
Gsk3btm2Jrw/Gsk3btm2Jrw
Irs2tm1Mfw/Irs2tm1Mfw
Tg(Ins2-cre)23Herr/?
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gsk3btm2Jrw mutation (1 available); any Gsk3b mutation (97 available)
Irs2tm1Mfw mutation (1 available); any Irs2 mutation (10 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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




Genotype
MGI:5494970
cn11
Allelic
Composition
Cdh1tm2Kem/Cdh1tm2Kem
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdh1tm2Kem mutation (1 available); any Cdh1 mutation (157 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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/body
N
• mice exhibit normal body weight

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




Genotype
MGI:3832577
cn12
Allelic
Composition
Gt(ROSA)26Sortm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(Kcnj11*V59M)Fmas mutation (0 available); any Gt(ROSA)26Sor mutation (343 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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/body
• 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 ID Ref(s)
Diabetes Mellitus, Permanent Neonatal; PNDM 606176 J:144715




Genotype
MGI:3797790
cn13
Allelic
Composition
Tg(Ins2-cre)23Herr/0
Tsc2tm1Kido/Tsc2tm1Kido
Genetic
Background
involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-cre)23Herr mutation (0 available)
Tsc2tm1Kido mutation (0 available); any Tsc2 mutation (30 available)
phenotype observed in females
phenotype observed in males
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/body
• after 48 weeks of age




Genotype
MGI:3629034
cn14
Allelic
Composition
Foxo1tm1Whb/Foxo1+
Pdpk1tm1Maka/Pdpk1tm1Maka
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1tm1Whb mutation (0 available); any Foxo1 mutation (12 available)
Pdpk1tm1Maka mutation (0 available); any Pdpk1 mutation (119 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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




Genotype
MGI:3629033
cn15
Allelic
Composition
Pdpk1tm1Maka/Pdpk1tm1Maka
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S4/SvJae * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Pdpk1tm1Maka mutation (0 available); any Pdpk1 mutation (119 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• all male knockouts die between 12 and 24 weeks of age from uncontrolled diabetes

growth/size/body
• 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




Genotype
MGI:5297841
cn16
Allelic
Composition
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Gt(ROSA)26Sortm14(CAG-tdTomato)Hze/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S6/SvEvTac * Black Swiss * C57BL/6 * CBA/J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm14(CAG-tdTomato)Hze mutation (2 available); any Gt(ROSA)26Sor mutation (343 available)
Nkx2-2tm2.1Suss mutation (0 available); any Nkx2-2 mutation (4 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• beta cells are reprogrammed to alpha cells

cellular
• beta cells are reprogrammed to alpha cells




Genotype
MGI:5638417
cn17
Allelic
Composition
Foxo1tm1Rdp/Foxo1tm1Rdp
Foxo3tm1Rdp/Foxo3tm1Rdp
Foxo4tm1Rdp/Foxo4tm1Rdp
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6 * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1tm1Rdp mutation (1 available); any Foxo1 mutation (12 available)
Foxo3tm1Rdp mutation (1 available); any Foxo3 mutation (21 available)
Foxo4tm1Rdp mutation (1 available); any Foxo4 mutation (7 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• mice show a defect in glucose-dependent insulin secretion that leads to early-onset, mild and moderately progressive diabetes
• mice subjected to hyperglycemic clamps require an approximate 50% lower rate of glucose infusion to maintain steady-state hyperglycemia
• mice are impaired in secreting insulin in response to the ATP-dependent K-channel blocker, glibenclamide, and to the depolarizing agent, I-arginine
• beta cells exhibit reduced calcium-dependent insulin secretion
• purified islets show lower insulin secretion in response to the sulfonylurea glibenclamide, the PKC activator PMA, and the L-type Ca channel activator Bay-K8644
• mice exhibit hyperglycemia in the fasted, refed, and random-fed states as early as 12 weeks of age
• mice exhibit lower plasma insulin levels in fasted, refed, and random-fed states, although not significant in the latter state
• mice show impaired glucose tolerance that worsens progressively with age during intraperitoneal glucose tolerance tests, without changes to peripheral insulin sensitivity

endocrine/exocrine glands
• as mice age to 12 months, beta cell dedifferentiation occurs
• beta cells are metabolically inflexible such that they preferentially utilize lipids rather than carbohydrates as an energy source resulting in impaired ATP generation and reduced calcium-dependent insulin secretion
• glucose oxidation to carbon dioxide is impaired by about 50% in islets at most glucose concentrations
• palmitate oxidation by islets in the presence of basal glucose is 2-fold higher and nearly 2.5-fold higher in high glucose
• glycerolipid synthesis of islets is normal at low glucose concentrations but fails to increase at elevated glucose concentrations, resulting in lower conversion of palmitate into diacylglycerides and triglycerides indicating that beta cells appear to be locked in a lipid oxidative state
• membrane depolarization-induced calcium influx in response to rising glucose concentrations is lower in beta cells
• mice are impaired in secreting insulin in response to the ATP-dependent K-channel blocker, glibenclamide, and to the depolarizing agent, I-arginine
• beta cells exhibit reduced calcium-dependent insulin secretion
• purified islets show lower insulin secretion in response to the sulfonylurea glibenclamide, the PKC activator PMA, and the L-type Ca channel activator Bay-K8644

cellular
• as mice age to 12 months, beta cell dedifferentiation occurs
• islets show a decrease in glucose-induced oxygen consumption
• raising glucose levels does not increase ATP turnover in purified islets as in control islets

Mouse Models of Human Disease
OMIM ID Ref(s)
Maturity-Onset Diabetes of the Young; MODY 606391 J:215526




Genotype
MGI:5296660
cn18
Allelic
Composition
Kdm5atm1Kael/Kdm5atm1Kael
Men1tm2.1Mmey/Men1tm2.1Mmey
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6 * CBA/J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Kdm5atm1Kael mutation (1 available); any Kdm5a mutation (33 available)
Men1tm2.1Mmey mutation (0 available); any Men1 mutation (22 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• median survival is 69 weeks

endocrine/exocrine glands
N
• islet proliferation is normal
• 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
• in 2 of 21 mice at 10 months of age

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




Genotype
MGI:5296659
cn19
Allelic
Composition
Men1tm2.1Mmey/Men1tm2.1Mmey
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S6/SvEvTac * C57BL/6 * CBA/J * FVB/N
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Men1tm2.1Mmey mutation (0 available); any Men1 mutation (22 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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
• in 3 of 16 mice at 8 months of age
• in all mice at 10 months of age
• islet proliferation is increased compared to in control mice

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




Genotype
MGI:5297821
cn20
Allelic
Composition
Dnmt3atm1Jae/Dnmt3atm1Jae
Gt(ROSA)26Sortm1Sor/Gt(ROSA)26Sor+
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129S/Sv * Black Swiss * C57BL/6 * CBA/J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dnmt3atm1Jae mutation (1 available); any Dnmt3a mutation (106 available)
Gt(ROSA)26Sortm1Sor mutation (7 available); any Gt(ROSA)26Sor mutation (343 available)
Nkx2-2tm2.1Suss mutation (0 available); any Nkx2-2 mutation (4 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands
• mice exhibit beta to alpha cell transdifferentiation

cellular
• mice exhibit beta to alpha cell transdifferentiation




Genotype
MGI:3614209
cn21
Allelic
Composition
Wfs1tm1Perm/Wfs1tm1Perm
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: 129X1/SvJ * C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Tg(Ins2-cre)23Herr mutation (0 available)
Wfs1tm1Perm mutation (0 available); any Wfs1 mutation (22 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 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 ID Ref(s)
Wolfram Syndrome 1; WFS1 222300 J:104712




Genotype
MGI:5297820
cn22
Allelic
Composition
Dnmt3atm1Jae/Dnmt3atm1Jae
Nkx2-2tm2.1Suss/Nkx2-2tm2.1Suss
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: Black Swiss * C57BL/6 * CBA/J * SJL
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dnmt3atm1Jae mutation (1 available); any Dnmt3a mutation (106 available)
Nkx2-2tm2.1Suss mutation (0 available); any Nkx2-2 mutation (4 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
endocrine/exocrine glands




Genotype
MGI:4430413
cn23
Allelic
Composition
Gt(ROSA)26Sortm1(CAG-Kcnj11*,-GFP)Nich/Gt(ROSA)26Sor+
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: C57BL/6 * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gt(ROSA)26Sortm1(CAG-Kcnj11*,-GFP)Nich mutation (0 available); any Gt(ROSA)26Sor mutation (343 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
growth/size/body
• 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 ID Ref(s)
Diabetes Mellitus, Permanent Neonatal; PNDM 606176 J:146650




Genotype
MGI:5315853
cn24
Allelic
Composition
Huwe1tm1Wgu/Y
Tg(Ins2-cre)23Herr/0
Trp53tm1Thl/Trp53tm1Thl
Genetic
Background
involves: C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Huwe1tm1Wgu mutation (0 available); any Huwe1 mutation (66 available)
Tg(Ins2-cre)23Herr mutation (0 available)
Trp53tm1Thl mutation (0 available); any Trp53 mutation (146 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
N
• mice survive longer than Huwe1tm1Wgu/Y Tg(Ins2-cre)23Herr mice

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

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




Genotype
MGI:5315852
cn25
Allelic
Composition
Huwe1tm1Wgu/Y
Tg(Ins2-cre)23Herr/0
Genetic
Background
involves: C57BL/6J * CBA/J
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Huwe1tm1Wgu mutation (0 available); any Huwe1 mutation (66 available)
Tg(Ins2-cre)23Herr mutation (0 available)
phenotype observed in females
phenotype observed in males
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

homeostasis/metabolism
• in fasting and fed mice at 6 and 9 months of age
• progressive
• in fasting mice at 9 months
• in fed mice at 6 and 9 months
• at 3 and 6 months

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

renal/urinary system

growth/size/body
• at 9 months





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last database update
11/29/2016
MGI 6.06
The Jackson Laboratory