cn1

Arx^tm1Gldn/Arx^tm1Gldn
Nkx2-2^tm2.1Suss/Nkx2-2^tm2.1Suss
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	Euro	Europhenome
N	normal phenotype

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:177838 )

N	• beta cell do not transdifferentiate into alpha cells unlike in Nkx2-2^tm2.1Suss homozygotes (J:177838)

decreased pancreatic beta cell number ( J:177838 )

• at E18.5 (J:177838)

homeostasis/metabolism

hyperglycemia ( J:177838 )

(J:177838)

cn2

Cebpb^tm1.1Maka/Cebpb^tm1.1Maka
Ins2^Akita/Ins2^Akita
Tg(Ins2-cre)23Herr/0
involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA/J

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

Abnormal glucose and insulin homeostasis in Ins2^Akita/Ins2^Akita and Ins2^Akita/Ins2^Akita Cebpb^tm1.1Maka/Cebpb^tm1.1Maka Tg(Ins2-cre)23Herr/0 but not Cebpb^tm1.1Maka/Cebpb^tm1.1Maka Tg(Ins2-cre)23Herr/0 mice.

endocrine/exocrine glands

abnormal pancreatic islet cell apoptosis ( J:156725 )

• expression of apoptosis markers in the pancreas islet is decreased compared to in Ins2^Akita homozygotes

abnormal pancreatic beta cell mass ( J:156725 )

• mice exhibit improved beta cell mass compared to in Ins2^Akita homozygotes

decreased insulin secretion ( J:156725 )

• pancreatic insulin levels are decreased compared to in wild-type mice

• however, pancreatic insulin content is 8-fold higher than in Ins2^Akita homozygotes

homeostasis/metabolism

decreased insulin secretion ( J:156725 )

• pancreatic insulin levels are decreased compared to in wild-type mice

• however, pancreatic insulin content is 8-fold higher than in Ins2^Akita homozygotes

increased circulating glucose level ( J:156725 )

• mice exhibit increased circulating glucose levels compared to in wild-type mice

• however, glucose serum level are increased compared to in Ins2^Akita homozygotes

decreased circulating insulin level ( J:156725 )

• mice exhibit decreased circulating glucose levels compared to in wild-type mice

• however, insulin serum level are increased compared to in Ins2^Akita homozygotes

cellular

abnormal pancreatic islet cell apoptosis ( J:156725 )

• expression of apoptosis markers in the pancreas islet is decreased compared to in Ins2^Akita homozygotes

cn3

Gjd2^tm4Kwi/Gjd2^tm4Kwi
Tg(Ins2-cre)23Herr/?
involves: 129P2/OlaHsd * C57BL/6 * CBA

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:174834 )

• Cx36 channels are non functional as determined by "tracer" studies (beta cells are uncoupled)

increased insulin secretion ( J:174834 )

• increased basal secretion of insulin

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:174834 )

N	• normal in vivo tolerance for acute glucose load (J:174834) • normal responsiveness to high glucose levels (16mM) (J:174834)

increased insulin secretion ( J:174834 )

• increased basal secretion of insulin

abnormal glucose tolerance ( J:174834 )

• do not respond to physiological concentrations of glucose

cn4

Cebpb^tm1.1Maka/Cebpb^tm1.1Maka
Lepr^db/Lepr^db
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	Euro	Europhenome
N	normal phenotype

Increased beta cell mass in Lepr^db/Lepr^db mice and Lepr^db/Lepr^db Cebpb^tm1.1Maka/Cebpb^tm1.1Maka Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands

abnormal pancreatic islet cell apoptosis ( J:156725 )

• pancreatic islet cell apoptosis is decreased compared to in Lepr^db homozygotes

increased pancreatic beta cell mass ( J:156725 )

• compared to in Lepr^db homozygotes

homeostasis/metabolism

hyperglycemia ( J:156725 )

• hyperglycemia develops more slowly and is ameliorated compared to in Lepr^db homozygotes

increased circulating insulin level ( J:156725 )

• at 12 weeks, plasma insulin levels are increased compared to in Lepr^db homozygotes and wild-type mice

cellular

abnormal pancreatic islet cell apoptosis ( J:156725 )

• pancreatic islet cell apoptosis is decreased compared to in Lepr^db homozygotes

cn5

Men1^tm1.2Zqw/Men1^tm1.2Zqw
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	Euro	Europhenome
N	normal phenotype

tumorigenesis

increased insulinoma incidence ( J:85133 )

• 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

pancreatic islet hyperplasia ( J:85133 )

• hyperplastic islets as early as 2 months of age, which progresses with aging

homeostasis/metabolism

hypoglycemia ( J:85133 )

• glucose levels decreased after 8 months of agae, as tumorigenesis progressed

increased circulating insulin level ( J:85133 )

• 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

cn6

Cebpb^tm1.1Maka/Cebpb^tm1.1Maka
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	Euro	Europhenome
N	normal phenotype

Higher plasma insulin levels and increased pancreatic insulin content in Cebpb^tm1.1Maka/Cebpb^tm1.1Maka Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands

increased insulin secretion ( J:156725 )

• pancreas insulin levels are higher than in Cebpb^tm1.1Maka homozygotes

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:156725 )

N	• mice exhibit normal circulating insulin and glucose levels (J:156725)

increased insulin secretion ( J:156725 )

• pancreas insulin levels are higher than in Cebpb^tm1.1Maka homozygotes

cn7

Dnmt3a^tm1Jae/Dnmt3a^tm1Jae
Gt(ROSA)26Sor^tm1Sor/Gt(ROSA)26Sor⁺
Nkx2-2^tm2.1Suss/Nkx2-2^tm2.1Suss
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	Euro	Europhenome
N	normal phenotype

endocrine/exocrine glands

abnormal pancreatic beta cell differentiation ( J:177838 )

• mice exhibit beta to alpha cell transdifferentiation

cellular

abnormal pancreatic beta cell differentiation ( J:177838 )

• mice exhibit beta to alpha cell transdifferentiation

cn8

Glud1^tm1.1Pma/Glud1^tm1.1Pma
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	Euro	Europhenome
N	normal phenotype

Disorganized pancreatic islets in Glud1^tm1.1Pma/Glud1^tm1.1Pma Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands

disorganized pancreatic islets ( J:145558 )

• 67% of islets are disorganized compared to 30% in wild-type mice

• however, pancreas insulin content is normal

decreased insulin secretion ( 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

growth/size

growth/size phenotype ( J:145558 )

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

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:145558 )

N	• despite disruptions in stimulated insulin secretion, mice exhibit normal glucose homeostasis and age-dependent insulin resistance (J:145558)

decreased insulin secretion ( 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

decreased circulating insulin level ( J:145558 )

• 55% when in a fed state

abnormal enzyme/coenzyme activity ( J:145558 )

• glutamate dehydrogenase activity is reduced by 60% in islets compared to in wild-type mice

cn9

Gsk3b^tm2Jrw/Gsk3b^tm2Jrw
Irs2^tm1Mfw/Irs2^tm1Mfw
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	Euro	Europhenome
N	normal phenotype

homeostasis/metabolism

abnormal circulating glucose level ( J:135659 )

• fed blood glucose concentration were significantly reduced relative to that in Irs2^tm1Mfw homozygous mice, though remained slightly higher than normal control

increased circulating insulin level ( J:135659 )

• both fasting and fed insulin levels were higher than in wild-type mice similar to the level found in Irs2^tm1Mfw homozygous mice

cn10

Gt(ROSA)26Sor^{tm1(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	Euro	Europhenome
N	normal phenotype

Reduction in islet insulin content in Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}/Gt(ROSA)26Sor⁺ Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:144715 )

• the percentage of islet area occupied by beta cells is somewhat decreased

abnormal pancreatic alpha cell morphology ( J:144715 )

• alpha cells are not confined to the islet mantle

increased pancreatic alpha cell number ( J:144715 )

• relative increase in the number of alpha cells

abnormal pancreatic beta cell morphology ( J:144715 )

• some of the beta cells are irregularly shaped

decreased pancreatic beta cell number ( J:144715 )

• the percentage of beta cells is decreased

abnormal pancreatic beta cell physiology ( J:144715 )

• 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

decreased insulin secretion ( J:144715 )

• impairment in basal and both first and second-phase glucose induced insulin secretion

homeostasis/metabolism

decreased insulin secretion ( J:144715 )

• impairment in basal and both first and second-phase glucose induced insulin secretion

increased circulating glucose level ( J:144715 )

• elevated glucose levels develop by P3

• overt diabetes develops by 5 weeks of age

increased circulating glucagon level ( J:144715 )

• slightly elevated

decreased circulating insulin level ( J:144715 )

growth/size

decreased body weight ( J:144715 )

• seen in males by 4 to 6 weeks of age

renal/urinary system

polyuria ( J:144715 )

• 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

cn11

Tg(Ins2-cre)23Herr/0
Tsc2^tm1Kido/Tsc2^tm1Kido
involves: 129S4/SvJae * C57BL/6 * C57BL/6J * CBA/J

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

homeostasis/metabolism

hypoglycemia ( J:135811 )

• in a fed state from 4 until 32 weeks of age

increased circulating glucose level ( J:135811 )

• 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

decreased circulating insulin level ( J:135811 )

• after 40 weeks of age

• however, treatment of mice with rapamycin prevents the decrease in plasma insulin levels

increased circulating insulin level ( J:135811 )

• at 12 weeks of age until 32 weeks

improved glucose tolerance ( J:135811 )

• at 8 weeks of age

increased insulin sensitivity ( J:135811 )

• at 8 weeks of age

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:135811 )

• at 40 weeks of age, islet cell density is decreased compared to in wild-type mice

increased pancreatic beta cell mass ( J:135811 )

• 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

decreased pancreatic beta cell number ( J:135811 )

• 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

pancreatic islet hyperplasia ( J:135811 )

• at 6 weeks of age

growth/size

decreased body weight ( J:135811 )

• after 48 weeks of age

cn12

Pdpk1^tm1Maka/Pdpk1^tm1Maka
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	Euro	Europhenome
N	normal phenotype

mortality/aging

premature death ( J:109010 )

• all male knockouts die between 12 and 24 weeks of age from uncontrolled diabetes

growth/size

decreased body weight ( J:109010 )

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

homeostasis/metabolism

increased circulating glucose level ( J:109010 )

hyperglycemia ( J:109010 )

• mutants exhibit hyperglycemia with blood glucose levels greater than 500 mg/dl by 12-16 weeks of age

decreased circulating insulin level ( J:109010 )

• 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

abnormal pancreatic beta cell morphology ( J:109010 )

• beta cells proliferate much less in islets of null mice; proliferation is ~50% lower at 4 weeks and ~75% lower at 8 weeks

small pancreatic islets ( J:109010 )

• 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

abnormal pancreas physiology ( J:109010 )

• insulin content of the pancreas in null mice is lower than in control mice

cn13

Foxo1^tm1Whb/Foxo1⁺
Pdpk1^tm1Maka/Pdpk1^tm1Maka
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	Euro	Europhenome
N	normal phenotype

homeostasis/metabolism

decreased circulating glucose level ( J:109010 )

• 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

increased circulating insulin level ( J:109010 )

• plasma insulin level is significantly higher in double mutants compared to Pdk1-deficient mice

endocrine/exocrine glands

increased pancreatic beta cell number ( J:109010 )

• Foxo-haploinsufficiency results in a significant increase in beta cell number in double mutants

abnormal pancreas physiology ( J:109010 )

• 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 ID	Ref(s)
Diabetes Mellitus, Insulin-Dependent; IDDM		222100	J:109224

cn14

Nkx2-2^tm2.1Suss/Nkx2-2^tm2.1Suss
Gt(ROSA)26Sor^{tm14(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	Euro	Europhenome
N	normal phenotype

endocrine/exocrine glands

abnormal pancreatic beta cell differentiation ( J:177838 )

• beta cells are reprogrammed to alpha cells

cellular

abnormal pancreatic beta cell differentiation ( J:177838 )

• beta cells are reprogrammed to alpha cells

cn15

Men1^tm2.1Mmey/Men1^tm2.1Mmey
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	Euro	Europhenome
N	normal phenotype

mortality/aging

premature death ( J:175625 )

• median survival is 45 weeks

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:175625 )

• in 5 of 10 mice at 2 months of age

• in 4 of 9 mice at 4 months of age

pancreatic islet hyperplasia ( J:175625 )

• in 5 of 10 mice at 2 months of age

• in 4 of 9 mice at 4 months of age

abnormal pancreas physiology ( J:175625 )

• islet proliferation is increased compared to in control mice

tumorigenesis

increased insulinoma incidence ( J:175625 )

• in 3 of 16 mice at 8 months of age

• in all mice at 10 months of age

cn16

Kdm5a^tm1Kael/Kdm5a^tm1Kael
Men1^tm2.1Mmey/Men1^tm2.1Mmey
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	Euro	Europhenome
N	normal phenotype

mortality/aging

premature death ( J:175625 )

• median survival is 69 weeks

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:175625 )

N	• islet proliferation is normal (J:175625)

abnormal pancreatic islet morphology ( J:175625 )

• atypia in 2 of 16 mice at 8 months of age

pancreatic islet hyperplasia ( J:175625 )

• in 1 of 8 mice at 2 months of age

• in 3 of 16 mice at 8 months of age

tumorigenesis

increased insulinoma incidence ( J:175625 )

• in 2 of 21 mice at 10 months of age

cn17

Wfs1^tm1Perm/Wfs1^tm1Perm
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	Euro	Europhenome
N	normal phenotype

growth/size

decreased body weight ( J:104712 )

• at 24 weeks of age, but not at 16, have lower weights

homeostasis/metabolism

abnormal glucose homeostasis ( J:104712 )

• both fasting and fed glucose:insulin ratios are elevated

• develop diabetes

decreased insulin secretion ( J:104712 )

• impaired glucose-stimulated insulin secretion

hyperglycemia ( J:104712 )

• progressive development of hyperglycemia

• fed glucose concentrations are higher at 24 weeks of age, but mean fasted glucose concentrations are normal

decreased circulating insulin level ( J:104712 )

• fasting insulin levels are significantly reduced at 12 weeks of age and fed insulin levels are reduced at 12 and 24 weeks of age

impaired glucose tolerance ( J:104712 )

• 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

abnormal pancreatic islet morphology ( J:104712 )

• 2.5-fold increase in caspase 3-positive nuclei in islets, indicating increased apoptosis

decreased pancreatic beta cell mass ( J:104712 )

• reduction of beta cell mass is seen at 24 weeks of age

decreased pancreatic beta cell number ( J:104712 )

• reduction of the beta cell:pancreas ratio is seen at 24 weeks of age

disorganized pancreatic islets ( J:104712 )

• 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

abnormal pancreatic beta cell physiology ( J:104712 )

• secretory granules are reduced in beta cells and majority of cells exhibit abundant dilated ER, indicating increased ER stress in beta cells

decreased insulin secretion ( J:104712 )

• impaired glucose-stimulated insulin secretion

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

cn18

Dnmt3a^tm1Jae/Dnmt3a^tm1Jae
Nkx2-2^tm2.1Suss/Nkx2-2^tm2.1Suss
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	Euro	Europhenome
N	normal phenotype

endocrine/exocrine glands

increased pancreatic alpha cell number ( J:177838 )

decreased pancreatic beta cell number ( J:177838 )

cn19

Gt(ROSA)26Sor^{tm1(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	Euro	Europhenome
N	normal phenotype

growth/size

slow postnatal weight gain ( J:146650 )

• 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

decreased insulin secretion ( J:146650 )

• by 6 weeks of age loss of response to injected glucose

abnormal circulating glucose level ( J:146650 )

• dramatic lowering of glucose levels after insulin injection

hyperglycemia ( J:146650 )

• blood glucose is over 200mg/dl within 2 weeks of birth

• progressively increases to over 600mg/dl by 2 months

abnormal circulating glucagon level ( J:146650 )

decreased circulating glucagon level ( J:146650 )

• levels become undetectable as diabetes becomes more severe

increased circulating glucagon level ( J:146650 )

• significantly elevated early in diabetes development

decreased circulating insulin level ( J:146650 )

• plasma insulin levels decrease with time

endocrine/exocrine glands

abnormal pancreas morphology ( J:146650 )

abnormal pancreatic islet morphology ( J:146650 )

abnormal pancreatic alpha cell morphology ( J:146650 )

• alpha cells infiltrate center of islets after the onset of diabetes

decreased pancreatic alpha cell number ( J:146650 )

• are lost as diabetes becomes more severe

decreased pancreatic beta cell number ( J:146650 )

• beta cells are lost as diabetes develops

decreased pancreatic islet number ( J:146650 )

• number of islet is reduced by 50% early in diabetes and by more than 90% later

small pancreatic islets ( J:146650 )

• islet mass decreases to about 10% of controls

decreased pancreas weight ( J:146650 )

• pancreas weight relative to controls becomes reduced over time

• pancreas weight/body weight ratio is normal

abnormal pancreatic beta cell physiology ( J:146650 )

• insulin content of pancreas drops to about 10% of control levels

decreased insulin secretion ( J:146650 )

• 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

cn20

Huwe1^tm1Wgu/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	Euro	Europhenome
N	normal phenotype

mortality/aging

premature death ( J:182446 )

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

homeostasis/metabolism

increased circulating glucose level ( J:182446 )

• in fasting and fed mice at 6 and 9 months of age (J:182446)

hyperglycemia ( J:182446 )

• progressive (J:182446)

decreased circulating insulin level ( J:182446 )

• in fasting mice at 9 months (J:182446)

• in fed mice at 6 and 9 months (J:182446)

impaired glucose tolerance ( J:182446 )

• at 3 and 6 months (J:182446)

endocrine/exocrine glands

decreased pancreatic beta cell number ( J:182446 )

• at 6 months and worsening at 9 months (J:182446)

disorganized pancreatic islets ( 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

abnormal urinary bladder morphology ( J:182446 )

• enlarged bladder (J:182446)

polyuria ( J:182446 )

(J:182446)

growth/size

decreased body weight ( J:182446 )

• at 9 months (J:182446)

cn21

Huwe1^tm1Wgu/Y
Tg(Ins2-cre)23Herr/0
Trp53^tm1Thl/Trp53^tm1Thl
involves: C57BL/6J * CBA/J

Key:
♀	phenotype observed in females	WTSI	Wellcome Trust Sanger Institute
♂	phenotype observed in males	Euro	Europhenome
N	normal phenotype

mortality/aging

mortality/aging ( J:182446 )

N	• mice survive longer than Huwe1^tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:182446 )

N	• diabetic symptoms (serum glucose and insulin levels and glucose intolerance) observed in Huwe1^tm1Wgu/Y Tg(Ins2-cre)23Herr mice are improved (J:182446)

hyperglycemia ( J:182446 )

• in fasting mice at 9 months but not as severe as in Huwe1^tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)

• in fed mice at 3, 6 and 9 months but not as severe as in Huwe1^tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:182446 )

N	• islet organization is improved compared to in Huwe1^tm1Wgu/Y Tg(Ins2-cre)23Herr mice (J:182446)