Phenotypes associated with this allele

• Allele Symbol: Tg(Ins2-cre)25Mgn
• Allele Name: transgene insertion 25, Mark A Magnuson
• Allele ID: MGI:2176227
• Summary: 65 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Atf6^tm1Hota/Atf6^tm1Hota Tg(Ins2-cre)25Mgn/0	B6.Cg-Atf6^tm1Hota Tg(Ins2-cre)25Mgn	MGI:5614219
cn2	Cdkal1^tm1.1Tomik/Cdkal1^tm1.1Tomik Tg(Ins2-cre)25Mgn/0	B6.Cg-Cdkal1^tm1.1Tomik Tg(Ins2-cre)25Mgn	MGI:5301577
cn3	Slc1a2^tm1.1Ncd/Slc1a2^tm1.1Ncd Tg(Ins2-cre)25Mgn/0	B6.Cg-Slc1a2^tm1.1Ncd Tg(Ins2-cre)25Mgn	MGI:5576470
cn4	Vhl^tm1Lss/Vhl^tm1Lss Tg(Ins2-cre)25Mgn/0	either: (involves: 129X1/SvJ * C57BL/6 * DBA) or (involves: 129X1/SvJ * A/J * C57BL/6 * DBA)	MGI:3844062
cn5	Lipe^tm2Rze/Lipe^tm2Rze Tg(Ins2-cre)25Mgn/?	involves: 129 * C57BL/6 * DBA	MGI:3833129
cn6	Nkx6-1^tm1Jlr/Nkx6-1^tm1.1Msan Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor^+ Tg(Ins2-cre)25Mgn/0	involves: 129 * C57BL/6 * DBA * SJL	MGI:5501188
cn7	Pparg^tm1.1Gonz/Pparg^tm1.1Gonz Tg(Ins2-cre)25Mgn/0	involves: 129 * C57 * FVB	MGI:3045806
cn8	Gadd45gip1^tm2Kong/Gadd45gip1^tm2Kong Tg(Ins2-cre)25Mgn/0	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5637560
cn9	Gt(ROSA)26Sor^tm1(Gck)Ydor/Gt(ROSA)26Sor^+ Trp53^tm1Brn/Trp53^tm1Brn Tg(Ins2-cre)25Mgn/0	involves: 129P2/OlaHsd * C57BL/6 * DBA	MGI:5581817
cn10	Gt(ROSA)26Sor^tm1(ptxA)Cgh/Gt(ROSA)26Sor^+ Tg(Ins2-cre)25Mgn/0	involves: 129P2/OlaHsd * C57BL/6 * DBA/2	MGI:3784868
cn11	Dlk1^tm1.1Jvs/Dlk1^+ Tg(Ins2-cre)25Mgn/0	involves: 129P2/OlaHsd * C57BL/6 * DBA * FVB/N	MGI:5471938
cn12	Pdx1^tm1Cvw/Pdx1^tm4Cvw Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6 * DBA	MGI:3774583
cn13	Irs1^tm1Jos/Irs1^+ Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3510670
cn14	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0 Tg(Ins2-Irs2)13Mfw/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3510675
cn15	Irs2^tm2Mfw/Irs2^tm2Mfw Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3510669
cn16	Tfam^tm1Lrsn/Tfam^tm1Lrsn Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:2177640
cn17	Cacna1c^tm3Hfm/Cacna1c^tm3Hfm Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:2674123
cn18	Kif5b^tm1Njen/Kif5b^+ Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * C57BL/6 * C57BL/6N * DBA * SJL	MGI:4946373
cn19	Kif5b^tm1Njen/Kif5b^tm1.1Njen Tg(Ins2-cre)25Mgn/0	involves: 129S1/Sv * C57BL/6 * C57BL/6N * DBA * SJL	MGI:4946372
cn20	Nr2f2^tm1Vco/Nr2f2^+ Tg(Ins2-cre)25Mgn/0	involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA	MGI:3578329
cn21	Nr2f2^tm1Vco/Nr2f2^tm1Vco Tg(Ins2-cre)25Mgn/0	involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA	MGI:3578328
cn22	Selenot^tm1.1Ics/Selenot^tm1.1Ics Tg(Ins2-cre)25Mgn/0	involves: 129S2/SvPas * C57BL/6 * C57BL/6J * DBA	MGI:5544757
cn23	Pten^tm1Hwu/Pten^tm1Hwu Rictor^tm1.1Mgn/Rictor^tm1.1Mgn Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * 129S6/SvEvTac * BALB/c * C57BL/6 * DBA	MGI:5008147
cn24	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA	MGI:5008144
cn25	Ghr^tm1.1Dlr/Ghr^tm1.1Dlr Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C3H * C57BL/6 * DBA	MGI:5056130
cn26	Irs2^tm2Tka/Irs2^tm2Tka Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6	MGI:3510986
cn27	Lepr^db/Lepr^db Pten^tm1Hwu/Pten^tm1Hwu Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA	MGI:5013485
cn28	Pten^tm1Hwu/Pten^tm1Hwu Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:4839070
cn29	Ffar2^tm2Soff/Ffar2^tm2Soff Ffar3^tm2.1Soff/Ffar3^tm2.1Soff Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA	MGI:5770569
cn30	Insr^tm1Khn/Insr^tm1Khn Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+ Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3775382
cn31	Insr^tm1Khn/Insr^tm1Khn Tg(Ins2-cre)25Mgn/0	involves: 129S4/SvJae * C57BL/6 * DBA/2	MGI:3775383
cn32	Rictor^tm1.1Mgn/Rictor^tm1.1Mgn Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA	MGI:5008146
cn33	Stat5b^tm1Mam/Stat5b^tm1Mam Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:4840006
cn34	Stat5a^tm2Mam/Stat5a^tm2Mam Stat5b^tm1Mam/Stat5b^tm1Mam Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:4840005
cn35	Bcl2l1^tm1.1Mam/Bcl2l1^tm1.1Mam Tg(Ins2-cre)25Mgn/0 Tg(RIP1-Tag)2Dh/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3843604
cn36	Chrm3^tm2Jwe/Chrm3^tm2Jwe Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3770245
cn37	Neurog3^tm1(Neurog3,cre/ERT)Ggu/Neurog3^tm1.1(cre/ERT)Ggu Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3850075
cn38	Neurog3^tm1(Neurog3,cre/ERT)Ggu/Neurog3^tm1(Neurog3,cre/ERT)Ggu Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * DBA	MGI:3850072
cn39	Gck^tm1.1Mgn/Gck^tm1.1Mgn Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:3603003
cn40	Gck^tm1.1Mgn/Gck^+ Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * DBA/2	MGI:3603012
cn41	Men1^tm1.2Ctre/Men1^tm1.2Ctre Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:3603666
cn42	Men1^tm1.2Ctre/Men1^+ Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:3603668
cn43	Irs2^tm1With/Irs2^tm1With Tg(Ins2-cre)25Mgn/0	involves: 129S6/SvEvTac * C57BL/6J	MGI:3576499
cn44	Akap5^tm1Jsco/Akap5^tm1Jsco Tg(Ins2-cre)25Mgn/0	involves: 129S * C57BL/6 * DBA	MGI:5448699
cn45	Opa1^tm1.1Hise/Opa1^tm1.2Hise Tg(Ins2-cre)25Mgn/0	involves: 129S/SvEv * C57BL/6 * DBA * SJL	MGI:5317794
cn46	Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz Tg(Ins2-cre)25Mgn/0	involves: 129/Sv * C57BL/6 * DBA/2	MGI:3775384
cn47	Prkci^tm1Kido/Prkci^tm1Kido Tg(Ins2-cre)25Mgn/0	involves: 129/Sv * C57BL/6 * DBA/2	MGI:3527979
cn48	Men1^tm1Gfk/Men1^tm1Gfk Tg(Ins2-cre)25Mgn/0	involves: 129T2/SvEms * C57BL/6 * C57BL/6J * DBA	MGI:3839791
cn49	Fasn^tm1Sem/Fasn^tm1Sem Tg(Ins2-cre)25Mgn/?	involves: 129X1/SvJ * C57BL/6 * DBA	MGI:3765153
cn50	Hnf4a^tm1.1Gonz/Hnf4a^tm1.1Gonz Tg(Ins2-cre)25Mgn/0	involves: 129X1/SvJ * C57BL/6 * DBA	MGI:3653173
cn51	Hmox1^tm1.1Hes/Hmox1^tm1.1Hes Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA	MGI:5660652
cn52	Gck^tm1Ydor/Gck^+ Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * C57BL/6J * DBA	MGI:6690664
cn53	Ier3ip1^tm1Arvn/Ier3ip1^tm1Arvn Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * C57BL/6J * DBA	MGI:7620429
cn54	Slc30a8^tm1.1Htwt/Slc30a8^tm1.1Htwt Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * CBA/JNCrlj * DBA	MGI:5558089
cn55	Atf6^tm1Hota/Atf6^tm1Hota Tg(Ins2-cre)25Mgn/0 Tg(Ins2-GP)1Kbuw/0	involves: C57BL/6 * DBA	MGI:5614220
cn56	Prkar2b^tm3Gsm/Prkar2b^tm2Gsm Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * DBA	MGI:5515338
cn57	Lamtor5^tm1Lye/Lamtor5^tm1Lye Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * DBA	MGI:6369091
cn58	Gt(ROSA)26Sor^tm1(Irx3*)Hui/Gt(ROSA)26Sor^+ Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * DBA	MGI:5616240
cn59	Gt(ROSA)26Sor^tm1(Gck)Ydor/Gt(ROSA)26Sor^+ Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * DBA	MGI:5581816
cn60	Igs2^em5(CAG-Mir802)Gpt/Igs2^em5(CAG-Mir802)Gpt Tg(Ins2-cre)25Mgn/0	involves: C57BL/6JGpt * DBA	MGI:6456820
cn61	Mir802^em3Gpt/Mir802^em3Gpt Tg(Ins2-cre)25Mgn/0	involves: C57BL/6JGpt * DBA	MGI:6456819
cn62	Fas^tm1Vbo/Fas^tm1Vbo Tg(Ins2-cre)25Mgn/0 Tg(Ins2-HA)165Bri/0 Tg(Tcra/Tcrb)1Vbo/0	Not Specified	MGI:2680187
cx63	Gt(ROSA)26Sor^tm1.1(Mir26a-1)Coh/Gt(ROSA)26Sor^+ Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * DBA	MGI:6402899
tg64	Tg(Ins2-cre)25Mgn/0	either: (B6.Cg-Tg(Ins2-cre)25Mgn/J) or (involves: 129 * C57BL/6 * DBA/2)	MGI:4941870
tg65	Tg(Ins2-cre)25Mgn/0	involves: C57BL/6 * DBA	MGI:4840008

Genotype
MGI:5614219

cn1

• Allelic Composition: Atf6^tm1Hota/Atf6^tm1Hota; Tg(Ins2-cre)25Mgn/0
• Genetic Background: B6.Cg-Atf6^tm1Hota Tg(Ins2-cre)25Mgn

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

increased insulin sensitivity ( J:213542 )

• slightly with lower insulin secretion curve in a glucose stimulated insulin secretion assay

decreased physiological sensitivity to xenobiotic ( J:213542 )

• increased cell death in primary islets that is not decreased in the presence of TUDCA

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:213542 )

N • beta cells develop normally

increased pancreatic islet cell apoptosis ( J:213542 )

• increased cell death in primary islets that is not decreased in the presence of TUDCA

growth/size/body

growth/size/body region phenotype ( J:213542 )

N • mice exhibit normal body weight

cellular

increased pancreatic islet cell apoptosis ( J:213542 )

• increased cell death in primary islets that is not decreased in the presence of TUDCA

Genotype
MGI:5301577

cn2

• Allelic Composition: Cdkal1^tm1.1Tomik/Cdkal1^tm1.1Tomik; Tg(Ins2-cre)25Mgn/0
• Genetic Background: B6.Cg-Cdkal1^tm1.1Tomik Tg(Ins2-cre)25Mgn

Endoplasmic reticulum distention in Cdkal1^tm1.2Tomik/Cdkal1^tm1.2Tomik Tg(Ins2-cre)25Mgn/0 beta cells

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:178248 )

• the number of small islets is lower and the number of large islets is greater than in control mice

• however, the total number of islets is normal

abnormal pancreatic beta cell physiology ( J:178248 )

• beta cells exhibit endoplasmic reticulum stress unlike control cells

• beta cells exhibit decreased glucose-stimulated ATP synthesis compared with control cells

abnormal insulin secretion ( J:178248 )

• the first-phase of insulin secretion is impaired

• however, the second-phase is normal

decreased insulin secretion ( J:178248 )

• in beta cells 15 minutes after glucose challenge

• following prostprandial stimulation

• in mice fed a high-fat diet

homeostasis/metabolism

abnormal insulin secretion ( J:178248 )

• the first-phase of insulin secretion is impaired

• however, the second-phase is normal

decreased insulin secretion ( J:178248 )

• in beta cells 15 minutes after glucose challenge

• following prostprandial stimulation

• in mice fed a high-fat diet

increased circulating glucose level ( J:178248 )

• in fasting and nonfasting mice fed a high-fat diet

impaired glucose tolerance ( J:178248 )

• at 5 to 10 weeks of age

• in mice fed a high-fat diet

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:178248

Genotype
MGI:5576470

cn3

• Allelic Composition: Slc1a2^tm1.1Ncd/Slc1a2^tm1.1Ncd; Tg(Ins2-cre)25Mgn/0
• Genetic Background: B6.Cg-Slc1a2^tm1.1Ncd Tg(Ins2-cre)25Mgn

normal phenotype

no abnormal phenotype detected ( J:207177 )

• mice show normal body weights and appearance and show no differences in glucose tolerance

Genotype
MGI:3844062

cn4

• Allelic Composition: Vhl^tm1Lss/Vhl^tm1Lss; Tg(Ins2-cre)25Mgn/0
• Genetic Background: either: (involves: 129X1/SvJ * C57BL/6 * DBA) or (involves: 129X1/SvJ * A/J * C57BL/6 * DBA)

mortality/aging

mortality/aging ( J:148174 )

N • expected Mendelian numbers of offspring are detected at weaning; no obvious behavioral or physiological abnormalities are detected

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:148174 )

N • pancreases appears histologically normal compared to controls from 10-23 months

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
von Hippel-Lindau disease		DOID:14175	OMIM:193300	J:148174

Genotype
MGI:3833129

cn5

• Allelic Composition: Lipe^tm2Rze/Lipe^tm2Rze; Tg(Ins2-cre)25Mgn/?
• Genetic Background: involves: 129 * C57BL/6 * DBA

homeostasis/metabolism

increased circulating leptin level ( J:144744 )

• 3.5 fold increase in plasma leptin

abnormal glucose homeostasis ( J:144744 )

• impaired insulin and glucagon response to challenge with arginine

• insulin tolerance test suggests a slight improvement in glucose disposal

abnormal insulin secretion ( J:144744 )

• in a 10 minute static test cultured cells fail to respond to elevated glucose levels which will cause a 2.3 fold increase in insulin secretion by control cells

increased circulating glucose level ( J:144744 )

• basal plasma glucose levels are significantly elevated at 12 weeks

impaired glucose tolerance ( J:144744 )

• delayed glucose clearance in an intravenous glucose tolerance test of 12 week old fasted mice but not 12 week old fed mice

• initial insulin response is severely blunted in both fasted and fed mice

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:144744 )

• significantly increased beta cell insulin content

increased pancreatic beta cell mass ( J:144744 )

abnormal insulin secretion ( J:144744 )

• in a 10 minute static test cultured cells fail to respond to elevated glucose levels which will cause a 2.3 fold increase in insulin secretion by control cells

adipose tissue

increased percent body fat/body weight ( J:144744 )

• significantly increase in overall body fat although body mass remains normal

growth/size/body

decreased lean body mass ( J:144744 )

Genotype
MGI:5501188

cn6

• Allelic Composition: Nkx6-1^tm1Jlr/Nkx6-1^tm1.1Msan; Gt(ROSA)26Sor^tm1(EYFP)Cos/Gt(ROSA)26Sor⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129 * C57BL/6 * DBA * SJL

endocrine/exocrine glands

abnormal pancreatic beta cell differentiation ( J:195153 )

• maintenance of beta cell is impaired with conversion to delta cell fate

decreased pancreatic beta cell number ( J:195153 )

increased pancreatic delta cell number ( J:195153 )

cellular

abnormal pancreatic beta cell differentiation ( J:195153 )

• maintenance of beta cell is impaired with conversion to delta cell fate

Genotype
MGI:3045806

cn7

• Allelic Composition: Pparg^tm1.1Gonz/Pparg^tm1.1Gonz; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129 * C57 * FVB

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:89959 )

• islets in mutant mice are about twice the size of those in wild-type littermates primarily as a result of beta cell hyperplasia

• however, on a high fat diet a significantly smaller increase in beta cell mass is seen in mutant mice (8.3-fold in wild-type vs. 2.1-fols d in mutant mice) resulting in significantly lower beta cell mass in mutants compared to wild-type littermates

• no other significant differences between mutant and wild-type littermates were found

Genotype
MGI:5637560

cn8

• Allelic Composition: Gadd45gip1^tm2Kong/Gadd45gip1^tm2Kong; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:220742 )

• islet area is normal at 4 weeks of age but is decreased by 45% at 11 weeks of age

abnormal pancreatic beta cell morphology ( J:220742 )

• beta cells exhibit an increased number of mitochondria

• endoplasmic reticulum in beta cells is distended around swollen mitochondria

decreased pancreatic beta cell mass ( J:220742 )

• progressive loss of beta cell mass associated with autophagy

• treatment with the glucagon-like peptide 1 agonist, exenatide, does not increase beta cell proliferation or mass in mutants as in wild-type mice

decreased pancreatic beta cell number ( J:220742 )

• mice show extensive loss of insulin-positive beta cells at 11 weeks of age

abnormal pancreatic beta cell physiology ( J:220742 )

• pancreatic insulin content is reduced in mice by 20% at 4 weeks and by 68% at 11 weeks of age

• beta cells exhibit an increase in autophagosomes, indicating increased autophagy

decreased pancreatic beta cell proliferation ( J:220742 )

• mice show a decrease in cell proliferation of beta cells at 4 and 11 weeks of age

• however, level of apoptosis in islets is similar to wild-type levels

decreased insulin secretion ( J:220742 )

• insulin secretion from islets upon either glucose or KCl stimulation in reduced in 4 and 11 week old mutants

cellular

abnormal mitochondrial morphology ( J:220742 )

• mouse embryonic fibroblast (MEF) mitochondria exhibit structural abnormalities characterized by intra-cristal swelling and reduced electron density in the mitochondrial matrix

abnormal mitochondrial crista morphology ( J:220742 )

• MEF mitochondria exhibit intra-cristal swelling

abnormal mitochondrial matrix morphology ( J:220742 )

• electron density of mitochondrial matrix is reduced in MEFs

increased mitochondrial number ( J:220742 )

• beta cells exhibit an increased number of mitochondria

decreased pancreatic beta cell proliferation ( J:220742 )

• mice show a decrease in cell proliferation of beta cells at 4 and 11 weeks of age

• however, level of apoptosis in islets is similar to wild-type levels

abnormal mitochondrial physiology ( J:220742 )

• response of islets to carbonyl cyanide m-chlorophenyl hydrazine, a mitochondrial respiration uncoupler, is delayed and the maximum capacity is decreased

homeostasis/metabolism

decreased insulin secretion ( J:220742 )

• insulin secretion from islets upon either glucose or KCl stimulation in reduced in 4 and 11 week old mutants

decreased oxygen consumption ( J:220742 )

• glucose stimulation increases oxygen consumption rate by only 1.3-fold in mutant islets compared to 2.1-fold in wild-type islets

impaired glucose tolerance ( J:220742 )

• in a glucose tolerance test, mice develop glucose intolerance at 4 weeks of age, characterized by a decrease in insulin secretion in response to glucose stimulation

• however, insulin sensitivity remains normal at 11 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:220742

Genotype
MGI:5581817

cn9

• Allelic Composition: Gt(ROSA)26Sor^tm1(Gck)Ydor/Gt(ROSA)26Sor⁺; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA

mortality/aging

postnatal lethality, incomplete penetrance ( J:210493 )

• some mice die before 3 weeks

homeostasis/metabolism

hyperglycemia ( J:210493 )

• slightly less so than in Gt(ROSA)26Sor^tm1(Gck)Ydor/Gt(ROSA)26Sor⁺ Tg(Ins2-cre)25Mgn mice

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:210493 )

N • islet architecture and beta cells are preserved in newborns

Genotype
MGI:3784868

cn10

• Allelic Composition: Gt(ROSA)26Sor^tm1(ptxA)Cgh/Gt(ROSA)26Sor⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA/2

homeostasis/metabolism

abnormal glucose homeostasis ( J:130781 )

• unlike in wild-type mice, glucose and insulin levels are unresponsive to treatment with 3-iodothyronamine

hypoglycemia ( J:130781 )

increased circulating insulin level ( J:130781 )

• plasma insulin levels are 4- to 5-fold higher than in wild-type mice

• plasma insulin levels following administration of glucose increased 6.5-fold over basal levels compared to an increase of only 3-fold in similarly treated wild-type mice and peak insulin level achieved is 15-fold higher than in similarly treated wild-type mice

improved glucose tolerance ( J:130781 )

• glucose clearance is increased compared to in wild-type mice

• when fed a high fat diet, mice exhibit improved glucose tolerance and normal fasting blood glucose levels compared to wild-type mice

• unlike wild-type mice, treatment with SLIGRL does not alter plasma glucose levels

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:130781 )

N • despite altered glucose homeostasis, mice exhibit normal pancreatic islet cell size, number, histological appearance and cellular composition

Genotype
MGI:5471938

cn11

• Allelic Composition: Dlk1^tm1.1Jvs/Dlk1⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * DBA * FVB/N

mortality/aging

mortality/aging ( J:194130 )

N • mice exhibit normal survival

growth/size/body

growth/size/body region phenotype ( J:194130 )

N • mice exhibit normal growth

Genotype
MGI:3774583

cn12

• Allelic Composition: Pdx1^tm1Cvw/Pdx1^tm4Cvw; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6 * DBA

cellular

decreased pancreatic beta cell proliferation ( J:130389 )

• proliferation of insulin+ cells is decreased

increased pancreatic alpha cell proliferation ( J:130389 )

• proliferation of glucagon+ cells is increased

endocrine/exocrine glands

decreased pancreatic beta cell proliferation ( J:130389 )

• proliferation of insulin+ cells is decreased

increased pancreatic alpha cell proliferation ( J:130389 )

• proliferation of glucagon+ cells is increased

abnormal pancreas morphology ( J:130389 )

• proliferation of Pdx1- cells is decreased compared to in wild-type pancreas

increased pancreatic alpha cell number ( J:130389 )

• beginning at E18.5, the number of glucagon+ cells is increased

• by one month of age mice are overtly diabetic with increased numbers of glucagon+ cells

• proliferation of glucagon+ cells is increased

decreased pancreatic beta cell number ( J:130389 )

• the number of insulin+ cells decreases as the number of glucagon+ cells increases

• proliferation of insulin+ cells is decreased

• by one month of age mice are overtly diabetic with decreased insulin immunoreactivity in remaining insulin+ cells

increased pancreatic delta cell number ( J:130389 )

• by one month of age mice are overtly diabetic with increased numbers of somatostatin+ cells

disorganized pancreatic islets ( J:130389 )

• glucagon+ and somatostatin+ cells are scattered throughout the islet instead of localized to the periphery as in wild-type mice

homeostasis/metabolism

increased circulating glucose level ( J:130389 )

• as early as P1

decreased circulating insulin level ( J:130389 )

• insulin levels following administration of glucose are lower in males and females compared to wild-type mice

impaired glucose tolerance ( J:130389 )

• unlike male mice, females exhibit only mild glucose intolerance compared to wild-type females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:130389

Genotype
MGI:3510670

cn13

• Allelic Composition: Irs1^tm1Jos/Irs1⁺; Irs2^tm2Mfw/Irs2^tm2Mfw; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:93415 )

• at 6 months beta cell content is decreased 8-fold

growth/size/body

decreased body weight ( J:93415 )

homeostasis/metabolism

hyperglycemia ( J:93415 )

• diabetes and progressive severe hyperglycemia are seen starting at 4 weeks of age

decreased circulating insulin level ( J:93415 )

• severe, progressive hypoinsulinemia is seen

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:93415

Genotype
MGI:3510675

cn14

• Allelic Composition: Irs2^tm2Mfw/Irs2^tm2Mfw; Tg(Ins2-cre)25Mgn/0; Tg(Ins2-Irs2)13Mfw/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

growth/size/body

increased body weight ( J:93415 )

• compound mutants continue to gain excess weight

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:93415 )

N • compound mutants do not develop hyperglycemia

Genotype
MGI:3510669

cn15

• Allelic Composition: Irs2^tm2Mfw/Irs2^tm2Mfw; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

pigmentation

abnormal coat/hair pigmentation ( J:93415 )

• mutants closely resemble agouti mice or mice deficient in Pmoc1 or Mcr4

adipose tissue

increased total body fat amount ( J:93415 )

• body fat is increased 2-fold, a disproportionate increase relative to the increase in body weight

behavior/neurological

polydipsia ( J:93415 )

• mutants drink 65% more water than wild-type mice

polyphagia ( J:93415 )

• mutants consume 60% more food than wild-type mice

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:93415 )

• the number of beta cells does not increase from 4 to 8 weeks of age unlike in wild-type mice, however by 6 months beta cell numbers are normal as a result of proliferation of cells that escaped cre mediated recombination

growth/size/body

increased body weight ( J:93415 )

• increased body weight is seen after 4 weeks of age with mutants weighing 30% more than wild-type mice at 32 weeks of age

• lean mass and total body fat are increased relative to wild-type mice

increased body length ( J:93415 )

• mutants are 10% longer than wild-type mice

homeostasis/metabolism

increased circulating glucose level ( J:93415 )

• fasting and random-fed glucose levels are elevated

increased circulating insulin level ( J:93415 )

• serum insulin is increased 2-fold, however pancreatic insulin levels were decreased more than 2-fold

• increased circulating insulin levels are also seen on a low fat diet

increased circulating leptin level ( J:93415 )

• serum leptin is increased 2-fold

impaired glucose tolerance ( J:93415 )

• glucose intolerance is seen on a normal or low fat diet

insulin resistance ( J:93415 )

• glucose clearance rates were decreased about 50% indicating peripheral insulin resistance

integument

abnormal coat/hair pigmentation ( J:93415 )

• mutants closely resemble agouti mice or mice deficient in Pmoc1 or Mcr4

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:93415

Genotype
MGI:2177640

cn16

• Allelic Composition: Tfam^tm1Lrsn/Tfam^tm1Lrsn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

decreased insulin secretion ( J:65522 )

• impaired

abnormal circulating insulin level ( J:65522 )

• decreased blood insulin concentration, onset at 5 week of age

increased insulin sensitivity ( J:65522 )

• onset at 27-33 weeks

endocrine/exocrine glands

absent pancreatic beta cells ( J:65522 )

• normal numbers at 7 weeks, absent at 37 weeks

decreased insulin secretion ( J:65522 )

• impaired

cellular

abnormal mitochondrial morphology ( J:65522 )

decreased mitochondrial DNA content ( J:65522 )

• mitochondrial DNA depletion

abnormal respiratory electron transport chain ( J:65522 )

• respiratory chain dysfunction in pancreatic islets

Genotype
MGI:2674123

cn17

• Allelic Composition: Cacna1c^tm3Hfm/Cacna1c^tm3Hfm; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

decreased insulin secretion ( J:84919 )

• intraperitoneal glucose challenge in fed mice results in a slight reduction in plasma insulin levels and marked reduction of glucose-induced first-phase insulin secretion

• glucose-induced first phase (less than 5 min) insulin secretion in in situ pancreatic perfusions is inhibited by 78%

• glucose-induced insulin secretion in isolated islets is much lower than in control islets

increased circulating glucose level ( J:84919 )

• mutants exhibit a slight hyperglycemia under basal and fasted conditions

decreased circulating insulin level ( J:84919 )

• intraperitoneal glucose challenge in fed mice results in a slight reduction in plasma insulin levels and marked reduction of glucose-induced first-phase insulin secretion

impaired glucose tolerance ( J:84919 )

• intraperitoneal glucose challenge in fed mice shows impaired glucose tolerance

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:84919 )

• calcium currents are reduced in beta cells from mutant mice

• exocytosis in response to the initial depolarizations is reduced in single beta cells

decreased insulin secretion ( J:84919 )

• intraperitoneal glucose challenge in fed mice results in a slight reduction in plasma insulin levels and marked reduction of glucose-induced first-phase insulin secretion

• glucose-induced first phase (less than 5 min) insulin secretion in in situ pancreatic perfusions is inhibited by 78%

• glucose-induced insulin secretion in isolated islets is much lower than in control islets

Genotype
MGI:4946373

cn18

• Allelic Composition: Kif5b^tm1Njen/Kif5b⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6N * DBA * SJL

homeostasis/metabolism

decreased insulin secretion ( J:170198 )

• slight after glucose injection

impaired glucose tolerance ( J:170198 )

• slight

endocrine/exocrine glands

decreased insulin secretion ( J:170198 )

• slight after glucose injection

Genotype
MGI:4946372

cn19

• Allelic Composition: Kif5b^tm1Njen/Kif5b^tm1.1Njen; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6N * DBA * SJL

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:170198 )

• mitochondria cluster in the perinuclear region unlike in wild-type beta cells

increased pancreatic beta cell number ( J:170198 )

small pancreatic islets ( J:170198 )

abnormal pancreas physiology ( J:170198 )

• islet cell proliferation is decreased compared to in control mice

• however, the rate of apoptosis is normal

abnormal pancreatic beta cell physiology ( J:170198 )

• mice exhibit an increase in insulin vesicles per cell area compared to in wild-type cells

decreased insulin secretion ( J:170198 )

• in early and slow phase after glucose injection

• after KCl-stimulation of islets

• however, insulin secretion is normal in the absence of glucose stimulation

homeostasis/metabolism

decreased insulin secretion ( J:170198 )

• in early and slow phase after glucose injection

• after KCl-stimulation of islets

• however, insulin secretion is normal in the absence of glucose stimulation

hyperglycemia ( J:170198 )

• progressive increase in random and 16-hour fasting conditions

decreased circulating insulin level ( J:170198 )

• in fasting conditions, but not in a random fed state

impaired glucose tolerance ( J:170198 )

• mice exhibit impaired glucose intolerance compared with wild-type mice

• however, blood glucose drops to wild-type levels 15 minutes after insulin injection

growth/size/body

decreased body weight ( J:170198 )

postnatal growth retardation ( J:170198 )

Genotype
MGI:3578329

cn20

• Allelic Composition: Nr2f2^tm1Vco/Nr2f2⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

abnormal glucose homeostasis ( J:98195 )

decreased insulin secretion ( J:98195 )

• virtually no insulin release in response to glucose challenge

increased insulin secretion ( J:98195 )

• slightly higher levels of release under basal conditions

decreased circulating glucose level ( J:98195 )

• slightly lower plasma glucose levels when fasted

• glucose levels normal when fed

increased circulating insulin level ( J:98195 )

• higher plasma insulin levels whether fed or fasted

• plasma insulin/glucagons ratio increased about 2X

• 20 minutes after glucose challenge, insulin levels are lower than in controls

impaired glucose tolerance ( J:98195 )

• glucose intolerant when tested on animals fasted overnight

• very high initial glucose levels after glucose challenge

insulin resistance ( J:98195 )

abnormal lipid level ( J:98195 )

increased circulating triglyceride level ( J:98195 )

• levels remain elevated when fed

decreased fatty acids level ( J:98195 )

• decreased free fatty acid levels when fasted

endocrine/exocrine glands

decreased insulin secretion ( J:98195 )

• virtually no insulin release in response to glucose challenge

increased insulin secretion ( J:98195 )

• slightly higher levels of release under basal conditions

Genotype
MGI:3578328

cn21

• Allelic Composition: Nr2f2^tm1Vco/Nr2f2^tm1Vco; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA

mortality/aging

prenatal lethality, complete penetrance ( J:98195 )

• death occurs before E18.5, possibly due to extrapancreatic cre expression

Genotype
MGI:5544757

cn22

• Allelic Composition: Selenot^tm1.1Ics/Selenot^tm1.1Ics; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S2/SvPas * C57BL/6 * C57BL/6J * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:203279 )

N • mice exhibit normal insulin sensitivity

decreased insulin secretion ( J:203279 )

• in the pancreas

increased circulating glucose level ( J:203279 )

decreased circulating insulin level ( J:203279 )

• after glucose load

• however, basal levels are normal

impaired glucose tolerance ( J:203279 )

endocrine/exocrine glands

increased pancreatic islet number ( J:203279 )

• increased number of small islets

• however, islet mass is normal

small pancreatic islets ( J:203279 )

• however, islet mass is normal

decreased insulin secretion ( J:203279 )

• in the pancreas

Genotype
MGI:5008147

cn23

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Rictor^tm1.1Mgn/Rictor^tm1.1Mgn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * BALB/c * C57BL/6 * DBA

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:170129 )

• average beta cell size is increased by 31% compared to controls and by 15% compared to single conditional Pten mutants

• however, mutants show normal beta cell proliferation

decreased pancreatic beta cell mass ( J:170129 )

• beta cell mass is about 40% lower than that of single conditional Pten mutants

growth/size/body

postnatal growth retardation ( J:170129 )

homeostasis/metabolism

abnormal glucose homeostasis ( J:170129 )

• total glucose excursion is lower compared to single conditional Rictor mutants

hypoglycemia ( J:170129 )

• fed blood glucose concentration remains similar to the controls, however mutants show a lower blood glucose concentration at 30 and 60 min after an intraperitoneal glucose bolus compared to single conditional Rictor mutants

decreased circulating insulin level ( J:170129 )

• mutants exhibit lower plasma insulin levels 15 min after glucose challenge and lower total insulin output compared with controls

• however, insulin secretion by glucose stimulated islets is similar to controls and pancreatic insulin content is unchanged

Genotype
MGI:5008144

cn24

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:170129 )

• beta-cell size is increased by 15% compared to controls

• number of proliferating beta-cells is increased by 34% compared to controls

increased pancreatic beta cell mass ( J:170129 )

• beta-cell mass is 86% higher than controls after adjusting for body size

• however, pancreatic insulin content is unchanged and insulin sensitivity is normal

growth/size/body

postnatal growth retardation ( J:170129 )

Genotype
MGI:5056130

cn25

• Allelic Composition: Ghr^tm1.1Dlr/Ghr^tm1.1Dlr; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C3H * C57BL/6 * DBA

High fat diet-induced obesity causes impaired glucose tolerance and insulin secretion in Ghr^tm1.1Dlr/Ghr^tm1.1Dlr Tg(Ins2-cre)25Mgn/0 mice

endocrine/exocrine glands

decreased pancreatic beta cell proliferation ( J:173909 )

• mice fed a high-fat diet exhibit decreased beta cell proliferation compared with wild-type mice

decreased pancreatic beta cell mass ( J:173909 )

• mice fed a high-fat diet exhibit impaired beta cell hyperplasia compared with similarly treated wild-type mice

decreased insulin secretion ( J:173909 )

• following administration of a glucose bolus, mice exhibit reduced first phase of insulin secretion compared with wild-type mice

• following glucose stimulation in pancreas islets from mice fed a high-fat diet

• however, mice exhibit normal insulin secretion in response to a physiologic (meal) glucose exposure and arginine-stimulated insulin release

homeostasis/metabolism

decreased insulin secretion ( J:173909 )

• following administration of a glucose bolus, mice exhibit reduced first phase of insulin secretion compared with wild-type mice

• following glucose stimulation in pancreas islets from mice fed a high-fat diet

• however, mice exhibit normal insulin secretion in response to a physiologic (meal) glucose exposure and arginine-stimulated insulin release

increased circulating glucose level ( J:173909 )

• during a glucose tolerance test in mice fed a high-fat diet

cellular

decreased pancreatic beta cell proliferation ( J:173909 )

• mice fed a high-fat diet exhibit decreased beta cell proliferation compared with wild-type mice

Genotype
MGI:3510986

cn26

• Allelic Composition: Irs2^tm2Tka/Irs2^tm2Tka; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

adipose tissue

increased epididymal fat pad weight ( J:93416 )

• the mass of the epididymal fat pad is increased at 12 weeks of age

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:93416 )

• beta cell mass is significantly reduced with or without caloric restriction at 8 and 12 weeks of age

• however at 10 days of age beta cell mass is not reduced

growth/size/body

increased body weight ( J:93416 )

• body weights are significantly greater than controls by 5 weeks of age

obese ( J:93416 )

• on a regular or high fat diet mutants become obese, however pair fed mutants do not become obese

homeostasis/metabolism

increased circulating glucose level ( J:93416 )

• on a high fat diet but not regular chow fasting glucose levels are significantly elevated

increased circulating leptin level ( J:93416 )

• fasting serum leptin levels are significantly increased

increased circulating cholesterol level ( J:93416 )

increased circulating triglyceride level ( J:93416 )

impaired glucose tolerance ( J:93416 )

insulin resistance ( J:93416 )

• insulin resistance is seen in mutants without caloric restriction or on a high fat diet

decreased response to leptin ( J:93416 )

• suppression of food intake by exogenous leptin is decreased, suggesting leptin resistance

Genotype
MGI:5013485

cn27

• Allelic Composition: Lepr^db/Lepr^db; Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:170206 )

N • mutants are protected from developing diabetes, and despite severe insulin resistance, mutants remain euglycemic and show normal glucose tolerance

increased insulin secretion ( J:170206 )

• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Lepr^db mice

insulin resistance ( J:170206 )

• mutants exhibit a similar degree of insulin resistance as single Lepr^db mice

growth/size/body

increased body weight ( J:170206 )

• mutants exhibit a similar degree of weight gain as single homozygous Lepr^db mice

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:170206 )

• islets show similar degrees of hypertrophy and proliferation as those in single homozygous Lepr^db mice and do not show a further increase in beta-cell mass compared to the single Lepr^db mice

increased insulin secretion ( J:170206 )

• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Lepr^db mice

Genotype
MGI:4839070

cn28

• Allelic Composition: Pten^tm1Hwu/Pten^tm1Hwu; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

cellular

decreased cellular sensitivity to oxidative stress ( J:106937 )

• islets are protected from oxidative stress

increased pancreatic beta cell proliferation ( J:106937 )

• increase in beta-cell proliferation at E17.5

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:170206 )

• increase in beta cell size

• beta-cells maintain intact response to DNA-damaging stimuli unlike controls

increased pancreatic beta cell mass ( J:170206 )

• increase in beta cell mass, due to an increase in proliferation and in beta cell size

• however, mutants do not exhibit any further increase in beta-cell mass on a high-fat diet

increased pancreatic beta cell number ( J:106937 )

• number of insulin-producing cells is increased in islets

increased pancreatic islet number ( J:106937 )

• 1.5-fold increase in islet numbers

enlarged pancreatic islets ( J:106937 )

• 2-fold increase in islet size

abnormal pancreas physiology ( J:106937 )

• decrease in apoptotic rate during pancreas remodeling at P17

• however, pancreas exhibits normal islet functions

increased pancreatic beta cell proliferation ( J:106937 )

• increase in beta-cell proliferation at E17.5

increased insulin secretion ( J:170206 )

• after high-fat diet feeding, mutants maintain robust insulin secretion in response to glucose compared to controls which show attenuation of insulin secretion, indicating that mutant islets are protected against high-fat diet-induced beta-cell dysfunction

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:170206 )

N • despite weight gain, mutants are protected from high-fat diet-induced diabetes, remaining euglycemic and showing improved glucose tolerance than controls on a high-fat diet

increased insulin secretion ( J:170206 )

• after high-fat diet feeding, mutants maintain robust insulin secretion in response to glucose compared to controls which show attenuation of insulin secretion, indicating that mutant islets are protected against high-fat diet-induced beta-cell dysfunction

hypoglycemia ( J:106937 )

• hypoglycemia, however mice respond normally to a glucose challenge

improved glucose tolerance ( J:170206 )

• mutants are protected from high-fat diet-induced diabetes, remaining euglycemic and showing improved glucose tolerance than controls on a high-fat diet

increased insulin sensitivity ( J:170206 )

• increase in peripheral insulin sensitivity

decreased susceptibility to injury ( J:106937 )

• mice are protected from STZ-induced beta-cell injury and diabetes

growth/size/body

increased body weight ( J:170206 )

Genotype
MGI:5770569

cn29

• Allelic Composition: Ffar2^tm2Soff/Ffar2^tm2Soff; Ffar3^tm2.1Soff/Ffar3^tm2.1Soff; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA

homeostasis/metabolism

abnormal insulin secretion ( J:227939 )

• loss of acetate-induced PTX-sensitive inhibition of glucose stimulated insulin secretion

increased circulating insulin level ( J:227939 )

• in mice fed a high-fat diet

decreased circulating free fatty acids level ( J:227939 )

• in mice fed a high-fat diet

improved glucose tolerance ( J:227939 )

• in mice fed a high-fat diet

endocrine/exocrine glands

abnormal insulin secretion ( J:227939 )

• loss of acetate-induced PTX-sensitive inhibition of glucose stimulated insulin secretion

Genotype
MGI:3775382

cn30

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

premature death ( J:121640 )

• 82% of mice die by 6 weeks of age with some mice surviving a few weeks longer

homeostasis/metabolism

decreased insulin secretion ( J:121640 )

hyperglycemia ( J:121640 )

• mice develop hypoglycemia at 2 weeks of age that rapidly worsens by 6 weeks of age

• mice exhibit high fasting glucose serum levels

increased circulating insulin level ( J:121640 )

impaired glucose tolerance ( J:121640 )

insulin resistance ( J:121640 )

endocrine/exocrine glands

decreased insulin secretion ( J:121640 )

renal/urinary system

polyuria ( J:121640 )

• during terminal stages

behavior/neurological

polydipsia ( J:121640 )

• during terminal stages

digestive/alimentary system

digestive/alimentary phenotype ( J:121640 )

N • unlike mice null for Insr in beta cells mice, islet cell mass is not increased despite similar levels of elevated insulin levels

growth/size/body

decreased body weight ( J:121640 )

• mice develop severe diabetes and loss 30% of their body weight in terminal stages

Genotype
MGI:3775383

cn31

• Allelic Composition: Insr^tm1Khn/Insr^tm1Khn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * DBA/2

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:121640 )

• when fed a high fat diet, 30% of mice die by 16 weeks

premature death ( J:121640 )

• some mice die due to severe hyperglycemia

homeostasis/metabolism

decreased insulin secretion ( J:121640 )

hyperglycemia ( J:121640 )

• mice exhibit an increase in serum glucose level on a regular diet and a severe increase when fed a high fat diet

impaired glucose tolerance ( J:121640 )

• mice exhibit impaired glucose tolerance on a normal diet and severe intolerance when fed a high fat diet

• however, mice are not insulin resistant

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:121640 )

• mice exhibit decreased beta cell mass when fed a normal or high fat diet

decreased insulin secretion ( J:121640 )

Genotype
MGI:5008146

cn32

• Allelic Composition: Rictor^tm1.1Mgn/Rictor^tm1.1Mgn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:170129 )

• beta-cell mass is 28% lower than controls after adjusting for body size

• the reduction in beta cell mass is mainly due to a decrease in beta cell proliferation

• however, beta cell size is unaffected and islet number per pancreatic unit area is unchanged in mutants

abnormal pancreatic beta cell physiology ( J:170129 )

• pancreatic insulin content is about 50% less than controls

decreased pancreatic beta cell proliferation ( J:170129 )

• number of proliferating beta-cells is decreased by 26% compared to controls

decreased insulin secretion ( J:170129 )

• islets have approximately 70% lower insulin secretion in response to glucose than controls

• however, insulin sensitivity is normal

homeostasis/metabolism

abnormal glucose homeostasis ( J:170129 )

• total glucose excursion is higher compared to controls

decreased insulin secretion ( J:170129 )

• islets have approximately 70% lower insulin secretion in response to glucose than controls

• however, insulin sensitivity is normal

hyperglycemia ( J:170129 )

• mutants exhibit hyperglycemia beginning at 12 weeks of age

impaired glucose tolerance ( J:170129 )

• mutants show slower glucose clearance as indicated by elevated blood glucose concentrations at 15 and 30 min after an intraperitoneal glucose bolus

• impaired glucose tolerance is due to reduced pancreatic insulin content and impaired glucose-stimulated insulin secretion

cellular

decreased pancreatic beta cell proliferation ( J:170129 )

• number of proliferating beta-cells is decreased by 26% compared to controls

Genotype
MGI:4840006

cn33

• Allelic Composition: Stat5b^tm1Mam/Stat5b^tm1Mam; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

growth/size/body

obese ( J:127051 )

• mild obesity

• weigh on the average 20% more than their control littermates by 9 months of age

adipose tissue

increased total body fat amount ( J:127051 )

• elevated adipose tissue mass of female mice

• normal lean mass

homeostasis/metabolism

decreased insulin secretion ( J:127051 )

• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose

increased circulating glucose level ( J:127051 )

• slightly elevated serum glucose levels at 7 months of age

increased circulating leptin level ( J:127051 )

• higher serum leptin levels at 7 months of age

• normal serum insulin levels

increased circulating free fatty acids level ( J:127051 )

• higher serum free fatty acids levels at 7 months of age

impaired glucose tolerance ( J:127051 )

• higher glucose levels than the controls at all time points after glucose injection

• severity of impaired glucose response increases in both female and male mice as they age

• more severe than that seen in Tg(Ins2-cre)25Mgn mice

endocrine/exocrine glands

disorganized pancreatic islets ( J:127051 )

• disrupted architecture of islets as evidenced by the migration of glucagon-expressing alpha-cells into the central region of the islets

decreased insulin secretion ( J:127051 )

• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose

Genotype
MGI:4840005

cn34

• Allelic Composition: Stat5a^tm2Mam/Stat5a^tm2Mam; Stat5b^tm1Mam/Stat5b^tm1Mam; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

growth/size/body

obese ( J:127051 )

• mild obesity

• weigh on the average 20% more than their control littermates by 9 months of age

adipose tissue

increased total body fat amount ( J:127051 )

• elevated adipose tissue mass of female mice

• normal lean mass

homeostasis/metabolism

decreased insulin secretion ( J:127051 )

• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose

increased circulating glucose level ( J:127051 )

• slightly elevated serum glucose levels at 7 months of age

increased circulating leptin level ( J:127051 )

• higher serum leptin levels at 7 months of age

• normal serum insulin levels

increased circulating free fatty acids level ( J:127051 )

• higher serum free fatty acids levels at 7 months of age

impaired glucose tolerance ( J:127051 )

• higher glucose levels than the controls at all time points after glucose injection

• severity of impaired glucose response increases in both female and male mice as they age

• more severe than that seen in Tg(Ins2-cre)25Mgn mice

endocrine/exocrine glands

disorganized pancreatic islets ( J:127051 )

• disrupted architecture of islets as evidenced by the migration of glucagon-expressing alpha-cells into the central region of the islets

decreased insulin secretion ( J:127051 )

• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose

Genotype
MGI:3843604

cn35

• Allelic Composition: Bcl2l1^tm1.1Mam/Bcl2l1^tm1.1Mam; Tg(Ins2-cre)25Mgn/0; Tg(RIP1-Tag)2Dh/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

neoplasm

increased pancreas tumor incidence ( J:146436 )

• 13 week old mice have a mean of over 4 tumors with an average volume greater than 50 mm³

• there is a significantly higher proportion of encapsulated, non-invasive tumors in these mice compared to Tg(RIP1-Tag)2Dh transgenics (22.8% vs. 4.3%)

endocrine/exocrine glands

increased pancreas tumor incidence ( J:146436 )

• 13 week old mice have a mean of over 4 tumors with an average volume greater than 50 mm³

• there is a significantly higher proportion of encapsulated, non-invasive tumors in these mice compared to Tg(RIP1-Tag)2Dh transgenics (22.8% vs. 4.3%)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
pancreatic carcinoma		DOID:4905	OMIM:260350	J:146436

Genotype
MGI:3770245

cn36

• Allelic Composition: Chrm3^tm2Jwe/Chrm3^tm2Jwe; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

homeostasis/metabolism

decreased insulin secretion ( J:129643 )

• insulin release following treatment with oxotremorine-M is reduced 50% compared to from wild-type islet cells

• however, total insulin content is normal

impaired glucose tolerance ( J:129643 )

• following administration of glucose, serum glucose levels are increased and insulin levels are decreased compared to in wild-type mice

• however, insulin sensitivity is normal

endocrine/exocrine glands

decreased insulin secretion ( J:129643 )

• insulin release following treatment with oxotremorine-M is reduced 50% compared to from wild-type islet cells

• however, total insulin content is normal

Genotype
MGI:3850075

cn37

• Allelic Composition: Neurog3^{tm1(Neurog3,cre/ERT)Ggu}/Neurog3^{tm1.1(cre/ERT)Ggu}; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

homeostasis/metabolism

increased circulating glucose level ( J:150074 )

• at 6 weeks compared to in Neurog3^{tm1(cre/ESR1)Ggu}/Neurog3^{tm1.1(cre/ESR1)Ggu} mice

Genotype
MGI:3850072

cn38

• Allelic Composition: Neurog3^{tm1(Neurog3,cre/ERT)Ggu}/Neurog3^{tm1(Neurog3,cre/ERT)Ggu}; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA

homeostasis/metabolism

increased circulating glucose level ( J:150074 )

• 13 weeks after birth

Genotype
MGI:3603003

cn39

• Allelic Composition: Gck^tm1.1Mgn/Gck^tm1.1Mgn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

mortality/aging

neonatal lethality, incomplete penetrance ( J:51826 )

• more than 80% neonatal mortality as a result of severe hyperglycemia

homeostasis/metabolism

hyperglycemia ( J:51826 )

• highly variable but increased blood glucose concentrations

decreased circulating insulin level ( J:51826 )

• decreased by about 70%

decreased liver glycogen level ( J:51826 )

• diminished hepatic glycogen

liver/biliary system

decreased liver glycogen level ( J:51826 )

• diminished hepatic glycogen

hepatic steatosis ( J:51826 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young type 2		DOID:0111100	OMIM:125851	J:51826

Genotype
MGI:3603012

cn40

• Allelic Composition: Gck^tm1.1Mgn/Gck⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

homeostasis/metabolism

decreased insulin secretion ( J:51826 )

• 70% decrease in insulin secretion during hyperglycemic clamp studies

hyperglycemia ( J:51826 )

• blood glucose concentration is increased by about 50% compared to heterozygous Gck^tm1.1Mgn mice

• under fasting conditions, have a 25% increase in blood glucose concentration, without differences in basal insulin concentration

impaired glucose tolerance ( J:51826 )

• glucose turnover and glucose infusion rates during hyperglycemic clamp are reduced by about 60 and 70%, respectively

decreased glycogen level ( J:51826 )

• net glycogen synthesis in liver is reduced by about 50% during hyperglycemic clamp studies

endocrine/exocrine glands

decreased insulin secretion ( J:51826 )

• 70% decrease in insulin secretion during hyperglycemic clamp studies

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young type 2		DOID:0111100	OMIM:125851	J:51826

Genotype
MGI:3603666

cn41

• Allelic Composition: Men1^tm1.2Ctre/Men1^tm1.2Ctre; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:85042 )

• abnormally large islets with pleomorphic cells of variable size and shape are seen at 4 weeks of age

• in 60 week old mutants islet volume has increased 20- to 26-fold

increased insulinoma incidence ( J:85042 )

• foci of adenoma develop within the hyperplastic islets by 20 - 28 weeks of age and multiple adenomas are seen by 23 weeks of age

• 19 of 34 homozygous floxed mutants had adenomas by the date of the scheduled autopsy and tumor incidence in homozygous mutants correlates to the level of Cre expression for the different cre transgenes

• a sex bias is seen with 13 of 16 virgin females developing adenomas compared to 6 of 18 males

homeostasis/metabolism

decreased circulating glucose level ( J:85042 )

• fasting blood glucose levels are decreased

increased circulating insulin level ( J:85042 )

• fasting serum insulin levels are increased

neoplasm

increased insulinoma incidence ( J:85042 )

• foci of adenoma develop within the hyperplastic islets by 20 - 28 weeks of age and multiple adenomas are seen by 23 weeks of age

• 19 of 34 homozygous floxed mutants had adenomas by the date of the scheduled autopsy and tumor incidence in homozygous mutants correlates to the level of Cre expression for the different cre transgenes

• a sex bias is seen with 13 of 16 virgin females developing adenomas compared to 6 of 18 males

Genotype
MGI:3603668

cn42

• Allelic Composition: Men1^tm1.2Ctre/Men1⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

neoplasm

increased insulinoma incidence ( J:85042 )

• heterozygous mutants develop islet tumors later than homozygous mutants

endocrine/exocrine glands

increased insulinoma incidence ( J:85042 )

• heterozygous mutants develop islet tumors later than homozygous mutants

Genotype
MGI:3576499

cn43

• Allelic Composition: Irs2^tm1With/Irs2^tm1With; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J

homeostasis/metabolism

increased circulating glucose level ( J:97406 )

• fasting blood glucose is moderately increased at 12 weeks and 6 months of age but not increased 4 weeks of age; however mutants do not display overt diabetes

increased circulating insulin level ( J:97406 )

• fasting hyperinsulinemia is seen at 12 weeks and 6 months of age

increased circulating leptin level ( J:97406 )

• at 12 weeks, but not 5 weeks, of age leptin levels are significantly elevated

impaired glucose tolerance ( J:97406 )

• defective glucose disposal is seen at 12 weeks and 6 months of age

endocrine/exocrine glands

decreased pancreatic beta cell number ( J:97406 )

• by 12 weeks of age beta cell mass is reduced by 40% compared to control mice

• at 9 months of age islet area is increased compared to 12 week old mutants but decreased compared to controls

growth/size/body

increased body weight ( J:97406 )

• body weight is increased by 4 - 5 weeks of age and 20% more by 12 weeks of age compared to controls

increased body length ( J:97406 )

behavior/neurological

polyphagia ( J:97406 )

• at 5 and 12 weeks of age food consumption is increased

Genotype
MGI:5448699

cn44

• Allelic Composition: Akap5^tm1Jsco/Akap5^tm1Jsco; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S * C57BL/6 * DBA

homeostasis/metabolism

increased insulin secretion ( J:190017 )

♂ • after intraperitoneal glucose injection in the pancreas

decreased circulating insulin level ( J:190017 )

♂ • in fasting mice and after intraperitoneal glucose injection

impaired glucose tolerance ( J:190017 )

♂ • despite normal insulin sensitivity

endocrine/exocrine glands

increased insulin secretion ( J:190017 )

♂ • after intraperitoneal glucose injection in the pancreas

Genotype
MGI:5317794

cn45

• Allelic Composition: Opa1^tm1.1Hise/Opa1^tm1.2Hise; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129S/SvEv * C57BL/6 * DBA * SJL

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:183074 )

N • following intraperitoneal insulin injection, mice exhibit normal insulin tolerance

decreased insulin secretion ( J:183074 )

• in glucose-stimulated beta cells and mice

• however, unstimulated insulin secretion is normal

increased circulating glucose level ( J:183074 )

• under fasted and fed conditions

• in a glucose tolerance test

decreased circulating insulin level ( J:183074 )

• following intraperitoneal glucose injection

decreased oxygen consumption ( J:183074 )

• in islets in response to glucose stimulation

impaired glucose tolerance ( J:183074 )

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:183074 )

• decreased beta cell size and density

decreased pancreatic beta cell number ( J:183074 )

• in adult mice

small pancreatic islets ( J:183074 )

abnormal pancreatic beta cell physiology ( J:183074 )

• newborn mice exhibit decreased beta cell proliferation compared with control mice

• glucose-stimulated beta cells secrete less insulin compared with control cells

• beta cells exhibit impaired glucose-stimulated ATP production compared with control cells

• however, beta cells exhibit normal apoptosis and unstimulated insulin secretion

decreased pancreatic beta cell proliferation ( J:183074 )

• newborn mice exhibit decreased beta cell proliferation compared with control mice

decreased insulin secretion ( J:183074 )

• in glucose-stimulated beta cells and mice

• however, unstimulated insulin secretion is normal

cellular

abnormal mitochondrial morphology ( J:183074 )

• mitochondria in beta cells are highly fragmented, shorter with wider cristae compared to in control cells

• however, volume density of mitochondria is normal

abnormal mitochondrial crista morphology ( J:183074 )

• wider in beta cells compared with control cells

decreased pancreatic beta cell proliferation ( J:183074 )

• newborn mice exhibit decreased beta cell proliferation compared with control mice

abnormal respiratory electron transport chain ( J:183074 )

• islets exhibit decreased complex IV activity compared with control cells

• however, activity levels of complex I is normal

Genotype
MGI:3775384

cn46

• Allelic Composition: Igf1r^tm1.1Mhz/Igf1r^tm1.1Mhz; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/2

mortality/aging

mortality/aging ( J:121640 )

N • mice do not exhibit an increase in mortality when fed a high fat diet

homeostasis/metabolism

hyperglycemia ( J:121640 )

• mild on a high fat diet

impaired glucose tolerance ( J:121640 )

• on a high fat diet

digestive/alimentary system

digestive/alimentary phenotype ( J:121640 )

N • when fed a high fat diet mice are capable of manifesting compensatory islet hyperplasia as in wild-type mice

Genotype
MGI:3527979

cn47

• Allelic Composition: Prkci^tm1Kido/Prkci^tm1Kido; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129/Sv * C57BL/6 * DBA/2

endocrine/exocrine glands

abnormal pancreas secretion ( J:95378 )

• islet insulin secretion is increased at low glucose concentrations (3-fold at 2.8 mM glucose) but decreased at high glucose concentrations (about 50% less at 16.8 mM) compared to control

• alpha and beta cell area are normal as is the total insulin content of the islets

homeostasis/metabolism

decreased circulating glucose level ( J:95378 )

• at 6 months, but not at 2 months, blood glucose concentrations are decreased in fasting mutants expressing cre compared to those without the cre transgene

impaired glucose tolerance ( J:95378 )

• on a normal or high fat diet blood glucose concentration 60 minutes after the glucose load is significantly higher and insulin response to glucose is impaired; however, insulin tolerance is not impaired

Genotype
MGI:3839791

cn48

• Allelic Composition: Men1^tm1Gfk/Men1^tm1Gfk; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129T2/SvEms * C57BL/6 * C57BL/6J * DBA

neoplasm

increased prolactinoma incidence ( J:89898 )

• by 12 months of age, 15 mice develop adenomas in the anterior pituitary gland that are prolactin positive

increased pancreas tumor incidence ( J:89898 )

• 7 of 21 mice develop pancreatic islet tumors that are positive for insulin

• islet tumors develop earlier and are more severe than those observed in Men1 knock-out heterozygotes

increased insulinoma incidence ( J:89898 )

endocrine/exocrine glands

pancreatic islet hyperplasia ( J:89898 )

• prominent in multiple islets consisting of beta cell hyperplasia

increased prolactinoma incidence ( J:89898 )

• by 12 months of age, 15 mice develop adenomas in the anterior pituitary gland that are prolactin positive

increased pancreas tumor incidence ( J:89898 )

• 7 of 21 mice develop pancreatic islet tumors that are positive for insulin

• islet tumors develop earlier and are more severe than those observed in Men1 knock-out heterozygotes

increased insulinoma incidence ( J:89898 )

nervous system

increased prolactinoma incidence ( J:89898 )

• by 12 months of age, 15 mice develop adenomas in the anterior pituitary gland that are prolactin positive

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
multiple endocrine neoplasia type 1		DOID:10017	OMIM:131100	J:89898

Genotype
MGI:3765153

cn49

• Allelic Composition: Fasn^tm1Sem/Fasn^tm1Sem; Tg(Ins2-cre)25Mgn/?
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA

growth/size/body

decreased body weight ( J:127482 )

• mice weigh less than littermate controls starting at 7 weeks of age for males and 13 weeks of age for females

• weight differences are due to decreased amounts of adipose tissue

homeostasis/metabolism

increased circulating glucose level ( J:127482 )

• glucose levels are about 20% higher than in wild-type mice fed the same amount of food

increased circulating insulin level ( J:127482 )

• levels are about 60% higher than in wild-type mice fed the same amount of food

increased circulating triglyceride level ( J:127482 )

• levels are about 55% higher than in wild-type mice fed the same amount of food

increased oxygen consumption ( J:127482 )

• is observed under both fed and fasted conditions

• increase in oxygen consumption is 20% higher than controls following a 24 hour fast

abnormal fatty acids level ( J:127482 )

• fatty acid synthase (FAS) enzyme activity in pancreatic islet cells is 30 fold less

• levels of the FAS substrate malonyl-CoA is elevated in islet cells and in the hypothalamus

decreased circulating free fatty acids level ( J:127482 )

• levels are about 41% lower than in wild-type mice fed the same amount of food

behavior/neurological

abnormal eating behavior ( J:127482 )

• freely fed mice consume 17% less food than controls

decreased compensatory feeding amount ( J:127482 )

• mice consume less than controls 4 hours and 24 hours after food is reintroduced after fasting

increased locomotor activity ( J:127482 )

• 20% to 300% increase in locomoter activity depending on timeframe and measuring methods that are used

adipose tissue

decreased total body fat amount ( J:127482 )

• 16-20 week old mice have about half the amount of adipose tissues as littermate controls

nervous system

abnormal hypothalamus physiology ( J:127482 )

• defects in fatty acid synthesis, which in turn lead to defects in PPARalpha signaling

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:127482 )

• defects in fatty acid synthesis

Genotype
MGI:3653173

cn50

• Allelic Composition: Hnf4a^tm1.1Gonz/Hnf4a^tm1.1Gonz; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * DBA

homeostasis/metabolism

decreased circulating insulin level ( J:108652 )

• at 10 weeks of age, females exhibit poor initial response of insulin secretion after receiving a glucose load; at 24 weeks, both males and females exhibit an impaired insulin response

• insulin secretion in response to high glucose levels is reduced in perfused islets from knockouts

impaired glucose tolerance ( J:108652 )

• glucose level at 12, 30, 60 and 120 minutes after administration of a glucose load are higher in females at 10 weeks compared to controls; at 24 weeks both males and females exhibit glucose intolerance

nervous system

abnormal channel response ( J:108652 )

• K_ATP activity is reduced in knockouts; decreased response leads to impaired insulin secretion

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young type 1		DOID:0111099	OMIM:125850	J:108652

Genotype
MGI:5660652

cn51

• Allelic Composition: Hmox1^tm1.1Hes/Hmox1^tm1.1Hes; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * C57BL/6N * DBA

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:214639 )

N • mice fed a high-fat diet exhibit similar body weight accumulation and glucose and insulin tolerance as controls

Genotype
MGI:6690664

cn52

• Allelic Composition: Gck^tm1Ydor/Gck⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA

homeostasis/metabolism

increased insulin secretion ( J:302600 )

• islets secrete more insulin per beta cell following glucose stimulation at 1.5 months and 8 months of age

• however, 8-month-old mice treated with diazoxide, an opener of the beta cell K-ATP channels and suppressor of endogenous insulin secretion, and subsequently administered insulin show a similar decrease in blood glucose levels as controls indicating no insulin resistance

decreased fasting circulating glucose level ( J:302600 )

• overnight fasted glucose levels are lower

• fasting glucose levels are lower in mice fed a high-fat/high-sugar diet

hypoglycemia ( J:302600 )

• mice exhibit reduced random blood glucose levels, which persists for at least 15 months

• mice fed a high-fat/high-sugar diet for 37 weeks exhibit consistently lower random glucose levels, however body weight gain is similar to controls

increased circulating insulin level ( J:302600 )

• plasma insulin levels are increased

• insulin levels are higher in mice fed a high-fat/high-sugar diet

impaired glucose tolerance ( J:302600 )

• mice exhibit impaired glucose tolerance at 8 months of age, while maintaining fed and fasting hypoglycemia

• however, no difference in glucose tolerance tests are seen at 1.5 months of age

• mice fed a high-fat/high-sugar diet for 37 weeks show more severely impaired glucose tolerance than controls

• after 37 weeks of a high-fat/high-sugar diet, peak insulin levels 15 minutes following glucose injection are slightly, but significantly, reduced despite identical blood glucose levels, indicating a subtle defect in first-phase insulin response

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:302600 )

• the increase in beta cell mass seen in high-fat/high-sugar diet-fed mice is attenuated in mutants

increased pancreatic beta cell mass ( J:302600 )

• 62% increase in beta cell mass at 1.5 months of age

• the 62% increase in beta cell mass seen at 1.5 months of age is completely reversed by 8 months of age; the proportion of cre+ beta cells is decreased from 71% in young mice to 48% in older mice

• however, individual beta cell volume is unchanged

abnormal endocrine pancreas physiology ( J:302600 )

• islets exhibit an increased membrane potential response at 2.8 mmol/l glucose

abnormal pancreatic beta cell physiology ( J:302600 )

• beta cells exhibit approximately a 2-fold increase in cell cycle entry accompanied by a 62% increase in beta cell mass at 1.5 months of age

• marker analysis indicates that with age beta cells show cellular stress, DNA damage and cell death over time

increased pancreatic beta cell proliferation ( J:302600 )

increased insulin secretion ( J:302600 )

• islets secrete more insulin per beta cell following glucose stimulation at 1.5 months and 8 months of age

• however, 8-month-old mice treated with diazoxide, an opener of the beta cell K-ATP channels and suppressor of endogenous insulin secretion, and subsequently administered insulin show a similar decrease in blood glucose levels as controls indicating no insulin resistance

cellular

increased pancreatic beta cell proliferation ( J:302600 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial hyperinsulinemic hypoglycemia 3		DOID:0070216	OMIM:602485	J:302600

Genotype
MGI:7620429

cn53

• Allelic Composition: Ier3ip1^tm1Arvn/Ier3ip1^tm1Arvn; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * C57BL/6J * DBA

growth/size/body

decreased body weight ( J:336782 )

• mice show a trend towards decreased body weight during the first 14 days of life

slow postnatal weight gain ( J:336782 )

• mice show impaired body weight gain starting from 11 weeks of age in male mice and 3 weeks of age in female mice

homeostasis/metabolism

abnormal glucose homeostasis ( J:336782 )

• both male and female mice develop early-onset insulin-deficient diabetes that becomes more severe at 3 weeks of age

decreased insulin secretion ( J:336782 )

• 3-wk-old mice show a significant reduction of proinsulin and insulin content in pancreatic islets

• absolute amount of secreted insulin in basal and glucose-stimulated conditions is dramatically reduced in proportion to the reduced insulin content

• however, glucose-stimulated proinsulin synthesis and glucose-stimulated insulin secretion (GSIS) are preserved

increased circulating glucose level ( J:336782 )

• mice exhibit a modest increase in blood glucose during the first 14 days of life

increased fasting circulating glucose level ( J:336782 )

• male and female mice show significantly higher fasting blood glucose levels than control littermates up to 16 weeks of age

hyperglycemia ( J:336782 )

• hyperglycemia progressively worsens over an observation period of 16 weeks

decreased circulating insulin level ( J:336782 )

• 3-wk-old male and female mice exhibit significantly lower fasting serum insulin levels than control littermates

impaired glucose tolerance ( J:336782 )

• 3-wk-old male and female mice exhibit significantly higher blood glucose levels than control littermates at all time points tested in oral glucose tolerance tests

endocrine/exocrine glands

increased pancreatic beta cell apoptosis ( J:336782 )

• pancreatic islets of 3-wk-old mice show significantly increased mRNA levels of Trib3 (a mediator of ER stress-induced cell death), along with a marked increase in nuclear chromatin condensation

• in contrast, mRNA levels of antiapoptotic genes (Bcl2l1 and Mcl1) are significantly suppressed

decreased pancreatic beta cell proliferation ( J:336782 )

• GO analyses of RNA-seq data show significant downregulation of biological pathways associated with cell proliferation in pancreatic islets from 3-wk-old mice

• Cdk1 (a core protein of the cell cycle) is significantly downregulated while immunostaining for Ki67 (a nuclear replication marker) is significantly reduced, suggesting decreased beta-cell proliferation

• in contrast, mRNA levels of cell growth inhibitors p21/Cdkn1a and p16/Cdkn2a are significantly upregulated

abnormal pancreatic beta cell morphology ( J:336782 )

• pancreatic beta cells of 3-wk-old mice show markedly dilated endoplasmic reticulum (ER) along with a significantly decreased insulin secretory granule number

• proinsulin is more diffusely distributed throughout the cytoplasm, unlike in wild-type beta cells where proinsulin is mostly localized in the juxtanuclear region

• ratio of proinsulin-positive/insulin-negative (Pro+Ins-) cells to total proinsulin positive (Pro+) cells is significantly increased, suggesting defective anterograde trafficking of proinsulin

abnormal pancreatic beta cell differentiation ( J:336782 )

• pancreatic islets of 3-wk-old mice show significantly reduced mRNA levels of key beta-cell transcription factors (Mafa, Pdx1, and Nkx6-1), along with significant decreases in PDX1 and NKX6-1 protein levels

• mRNA levels of Mafa and Pdx1 are decreased as early as at 2 weeks of age (before development of overt diabetes)

• islets show a significant increase in the abundance and intra-islet localization of glucagon+ cells as well as somatostatin+ cells along with a reduction in insulin+ cells, in addition to an increase in insulin+/glucagon+ double-positive cells and insulin+/somatostatin+ double-positive cells, indicating impaired beta-cell maturation and identity

decreased pancreatic beta cell mass ( J:336782 )

• pancreatic islets of 3-wk-old mice show a significant reduction in beta cell mass relative to control islets

small pancreatic islets ( J:336782 )

• pancreatic islets of 3-wk-old mice show a significant reduction in mean islet area relative to control islets

decreased insulin secretion ( J:336782 )

• 3-wk-old mice show a significant reduction of proinsulin and insulin content in pancreatic islets

• absolute amount of secreted insulin in basal and glucose-stimulated conditions is dramatically reduced in proportion to the reduced insulin content

• however, glucose-stimulated proinsulin synthesis and glucose-stimulated insulin secretion (GSIS) are preserved

cellular

abnormal endoplasmic reticulum morphology ( J:336782 )

• pancreatic beta cells show markedly dilated ER

increased pancreatic beta cell apoptosis ( J:336782 )

• pancreatic islets of 3-wk-old mice show significantly increased mRNA levels of Trib3 (a mediator of ER stress-induced cell death), along with a marked increase in nuclear chromatin condensation

• in contrast, mRNA levels of antiapoptotic genes (Bcl2l1 and Mcl1) are significantly suppressed

abnormal pancreatic beta cell differentiation ( J:336782 )

• pancreatic islets of 3-wk-old mice show significantly reduced mRNA levels of key beta-cell transcription factors (Mafa, Pdx1, and Nkx6-1), along with significant decreases in PDX1 and NKX6-1 protein levels

• mRNA levels of Mafa and Pdx1 are decreased as early as at 2 weeks of age (before development of overt diabetes)

• islets show a significant increase in the abundance and intra-islet localization of glucagon+ cells as well as somatostatin+ cells along with a reduction in insulin+ cells, in addition to an increase in insulin+/glucagon+ double-positive cells and insulin+/somatostatin+ double-positive cells, indicating impaired beta-cell maturation and identity

decreased pancreatic beta cell proliferation ( J:336782 )

• GO analyses of RNA-seq data show significant downregulation of biological pathways associated with cell proliferation in pancreatic islets from 3-wk-old mice

• Cdk1 (a core protein of the cell cycle) is significantly downregulated while immunostaining for Ki67 (a nuclear replication marker) is significantly reduced, suggesting decreased beta-cell proliferation

• in contrast, mRNA levels of cell growth inhibitors p21/Cdkn1a and p16/Cdkn2a are significantly upregulated

abnormal endoplasmic reticulum physiology ( J:336782 )

• pancreatic islets of 3-wk-old mice show impaired oxidative folding of proinsulin in the ER, as shown by markedly increased intermolecular disulfide-linked complexes (dimers, trimers, and high-molecular-weight proinsulin-associated complexes) under non-reducing conditions

increased endoplasmic reticulum stress ( J:336782 )

• pancreatic islets of 3-wk-old mice show a significant increase in both mRNA and protein levels of Hspa5 (aka BiP), along with a marked increase in protein levels of DNAJC3 (aka P58IPK), suggesting induced ER stress

• islets of 14- to 16-wk-old severely diabetic mice show significantly increased mRNA levels of ER stress markers (Hspa5 and Dnajc3)

• however, among genes involved in the unfolded protein response (UPR), only expression of Eif2ak3 (aka PERK) is moderately increased in severely diabetic mice, suggesting only a modest activation of UPR in beta cells

Genotype
MGI:5558089

cn54

• Allelic Composition: Slc30a8^tm1.1Htwt/Slc30a8^tm1.1Htwt; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * CBA/JNCrlj * DBA

liver/biliary system

liver/biliary system phenotype ( J:204003 )

N • mice exhibit normal liver function

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:204003 )

N • mice exhibit normal insulin tolerance, glucagon secretion and metabolic response to a high-fat diet

increased insulin secretion ( J:204003 )

• in mice fed chow or a high-fat diet

• twice as much as in control cells with a large portion of secreted insulin degraded through a single liver passage

impaired glucose tolerance ( J:204003 )

• mildly in mice fed chow

abnormal insulin clearance ( J:204003 )

• increased insulin clearance after glucose challenge

• proinsulin to insulin ratio is slightly higher than in wild-type mice

abnormal zinc homeostasis ( J:204003 )

• low zinc content in beta cell islets

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:204003 )

• insulin crystallization failure at 6 and 20 weeks with atypical insulin granules lacking a detectable dense core

• however, mice exhibit normal beta cell area and vessel structure and counts in islets

increased insulin secretion ( J:204003 )

• in mice fed chow or a high-fat diet

• twice as much as in control cells with a large portion of secreted insulin degraded through a single liver passage

Genotype
MGI:5614220

cn55

• Allelic Composition: Atf6^tm1Hota/Atf6^tm1Hota; Tg(Ins2-cre)25Mgn/0; Tg(Ins2-GP)1Kbuw/0
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:213542 )

• TUDCA-treated mice fail to exhibit a protective effect from diabetes with decreased insulin content and number of apoptotic cells in islets compared wild-type mice

Genotype
MGI:5515338

cn56

• Allelic Composition: Prkar2b^tm3Gsm/Prkar2b^tm2Gsm; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * DBA

behavior/neurological

behavior/neurological phenotype ( J:196157 )

N • hyperactivity phenotype is reduced

growth/size/body

growth/size/body region phenotype ( J:196157 )

N • body weight similar to controls

N • lean body mass is similar to controls

adipose tissue

adipose tissue phenotype ( J:196157 )

N • adiposity similar to controls

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:196157 )

N • serum leptin levels similar to controls

Genotype
MGI:6369091

cn57

• Allelic Composition: Lamtor5^tm1Lye/Lamtor5^tm1Lye; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * DBA

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:258406 )

• insulin content in isolated islets is decreased

decreased insulin secretion ( J:258406 )

• islets exhibit a decrease in glucose-stimulated insulin secretion that is more profound in islets from high-fat diet fed mice

homeostasis/metabolism

decreased insulin secretion ( J:258406 )

• islets exhibit a decrease in glucose-stimulated insulin secretion that is more profound in islets from high-fat diet fed mice

increased fasting circulating glucose level ( J:258406 )

• mice exhibit higher blood glucose levels in fasting conditions on both a normal chow diet and high-fat diet

decreased circulating insulin level ( J:258406 )

• both chow diet and high-fat diet fed mice show decreased circulating insulin levels

impaired glucose tolerance ( J:258406 )

• both chow diet and high-fat diet fed mice develop glucose intolerance upon intraperitoneal glucose administration, which is exacerbated when mice are obese

• however, mice exhibit normal insulin sensitivity

growth/size/body

growth/size/body region phenotype ( J:258406 )

N • mice exhibit normal body weight gain, food intake on a high-fat diet, and normal liver mass either on a normal chow diet or high fat diet

Genotype
MGI:5616240

cn58

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Irx3*)Hui}/Gt(ROSA)26Sor⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * DBA

growth/size/body

decreased body weight ( J:208887 )

• similar to mice homozygous for Irx3^tm1Hui

adipose tissue

decreased fat cell size ( J:208887 )

• similar to mice homozygous for Irx3^tm1Hui

decreased percent body fat/body weight ( J:208887 )

• similar to mice homozygous for Irx3^tm1Hui

abnormal white adipose tissue physiology ( J:208887 )

• expression analysis indicates browning of white adipose

homeostasis/metabolism

increased energy expenditure ( J:208887 )

• similar to mice homozygous for Irx3^tm1Hui

improved glucose tolerance ( J:208887 )

• similar to mice homozygous for Irx3^tm1Hui

behavior/neurological

behavior/neurological phenotype ( J:208887 )

N • food intake and locomotor activity are similar to controls

Genotype
MGI:5581816

cn59

• Allelic Composition: Gt(ROSA)26Sor^tm1(Gck)Ydor/Gt(ROSA)26Sor⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * DBA

mortality/aging

postnatal lethality, incomplete penetrance ( J:210493 )

• most mice die during the first week of life

homeostasis/metabolism

hyperglycemia ( J:210493 )

• at birth

decreased circulating insulin level ( J:210493 )

• mild at birth

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:210493 )

• reduced beta cell area at E16.5 and birth

Genotype
MGI:6456820

cn60

• Allelic Composition: Igs2^{em5(CAG-Mir802)Gpt}/Igs2^{em5(CAG-Mir802)Gpt}; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6JGpt * DBA

homeostasis/metabolism

decreased insulin secretion ( J:287584 )

• following exposure to glucose or 35 mM KCl

decreased circulating insulin level ( J:287584 )

• in mice after glucose injection

impaired glucose tolerance ( J:287584 )

• in mice challenged with IPGTT

• in islet cells exposed to glucose or 35 mM KCl

endocrine/exocrine glands

abnormal pancreatic beta cell differentiation ( J:287584 )

• reduced beta-cell differentiation as determined by marker expression

decreased pancreatic beta cell mass ( J:287584 )

• slight

decreased pancreatic beta cell number ( J:287584 )

decreased insulin secretion ( J:287584 )

• following exposure to glucose or 35 mM KCl

cellular

abnormal pancreatic beta cell differentiation ( J:287584 )

• reduced beta-cell differentiation as determined by marker expression

Genotype
MGI:6456819

cn61

• Allelic Composition: Mir802^em3Gpt/Mir802^em3Gpt; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6JGpt * DBA

homeostasis/metabolism

increased insulin secretion ( J:287584 )

• in islets from mice fed standard chow or a high-fat diet after glucose stimulation or treatment with 35 mM KCl

abnormal circulating insulin level ( J:287584 )

• mice fed a high-fat diet exhibit reduced serum insulin concentrations compared with control mice

increased circulating insulin level ( J:287584 )

• after glucose injection or fed a high-fat diet

improved glucose tolerance ( J:287584 )

• in mice challenged with IPGTT or fed a high-fat diet

endocrine/exocrine glands

abnormal pancreatic beta cell differentiation ( J:287584 )

• increased beta-cell differentiation as determined by marker expression

increased pancreatic beta cell number ( J:287584 )

increased insulin secretion ( J:287584 )

• in islets from mice fed standard chow or a high-fat diet after glucose stimulation or treatment with 35 mM KCl

cellular

abnormal pancreatic beta cell differentiation ( J:287584 )

• increased beta-cell differentiation as determined by marker expression

Genotype
MGI:2680187

cn62

• Allelic Composition: Fas^tm1Vbo/Fas^tm1Vbo; Tg(Ins2-cre)25Mgn/0; Tg(Ins2-HA)165Bri/0; Tg(Tcra/Tcrb)1Vbo/0
• Genetic Background: Not Specified

immune system

increased susceptibility to autoimmune diabetes ( J:85985 )

• autoimmune diabetes developed with accelerated kinetics

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 1 diabetes mellitus		DOID:9744	OMIM:222100	J:85985

Genotype
MGI:6402899

cx63

• Allelic Composition: Gt(ROSA)26Sor^{tm1.1(Mir26a-1)Coh}/Gt(ROSA)26Sor⁺; Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * DBA

endocrine/exocrine glands

decreased pancreatic beta cell mass ( J:286108 )

• when mice are fed a high-fat diet compared with controls

small pancreatic islets ( J:286108 )

• when mice are fed a high-fat diet compared with controls

decreased insulin secretion ( J:286108 )

• 3-fold from isolated islets treated with glucose

• however, response to arginine or KCl is normal and first-phase secretion is normal

homeostasis/metabolism

decreased insulin secretion ( J:286108 )

• 3-fold from isolated islets treated with glucose

• however, response to arginine or KCl is normal and first-phase secretion is normal

decreased susceptibility to diet-induced obesity ( J:286108 )

• when mice are fed a high-fat diet despite comparable food intake

decreased fasting circulating glucose level ( J:286108 )

• mice fed a high-fat diet exhibit reduced fasting glucose levels compared with control mice fed the same diet

decreased circulating insulin level ( J:286108 )

• mice fed a high-fat diet exhibit reduced insulin levels compared with control mice fed the same diet

improved glucose tolerance ( J:286108 )

• when mice are fed a high-fat diet compared with controls

increased insulin sensitivity ( J:286108 )

• when mice are fed a high-fat diet compared with controls

growth/size/body

decreased susceptibility to diet-induced obesity ( J:286108 )

• when mice are fed a high-fat diet despite comparable food intake

Genotype
MGI:4941870

tg64

• Allelic Composition: Tg(Ins2-cre)25Mgn/0
• Genetic Background: either: (B6.Cg-Tg(Ins2-cre)25Mgn/J) or (involves: 129 * C57BL/6 * DBA/2)

homeostasis/metabolism

abnormal insulin secretion ( J:108244 )

• transgenic mice appear to show impaired glucose-stimulated insulin secretion compared to wild-type controls after receiving a glucose injection; this is observed on a mixed and on a 95% B6 backgrounds

• the first phase of insulin secretion by 4 minutes after intraperitoneal injection of glucose appears to be absent in transgenic mice

abnormal circulating insulin level ( J:108244 )

• following intraperitoneal injection of glucose (3g/kg body weight), insulin levels in fasted transgenic mice (on mixed B6) background do not increase until 30 minutes after injection, whereas control mice show an immediate spike (>2-3 fold higher levels 2 minutes after injection) with elevated insulin levels persisting for over 30 minutes

• on a 95% B6 background, 36 week-old mice show no increase in serum insulin levels for about 60 minutes following intraperitoneal injection of glucose

• results indicated a loss of the first phase of insulin secretion by 4 minutes after intraperitoneal injection of glucose

impaired glucose tolerance ( J:108244 )

• at 2 months, mice show impaired glucose tolerance after intraperitoneal injection of glucose (2g/kg body weight) relative to control C57BL/6 (B6) mice but no difference in fasting blood glucose levels are seen; blood glucose (mg/dl) remains higher than levels in injected controls during the full 2 hour post-injection period

• glucose intolerance is more profound in females than males

• this is observed on a congenic (or 'pure') C57BL/6 background or on a mixed B6 background

• similar findings are observed independently in other labs where transgenic mice are on mixed (undetermined B6 contribution) or primarily C57BL/6 (95% B6) backgrounds; blood glucose levels remain elevated relative to controls for at least 30-60 minutes after glucose injection in transgenic mice at 6 or 18 weeks of age on a highly (95%) B6 background

endocrine/exocrine glands

abnormal insulin secretion ( J:108244 )

• transgenic mice appear to show impaired glucose-stimulated insulin secretion compared to wild-type controls after receiving a glucose injection; this is observed on a mixed and on a 95% B6 backgrounds

• the first phase of insulin secretion by 4 minutes after intraperitoneal injection of glucose appears to be absent in transgenic mice

Genotype
MGI:4840008

tg65

• Allelic Composition: Tg(Ins2-cre)25Mgn/0
• Genetic Background: involves: C57BL/6 * DBA

homeostasis/metabolism

decreased insulin secretion ( J:127051 )

• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose

impaired glucose tolerance ( J:127051 )

• glucose intolerance as early as 6 weeks of age

endocrine/exocrine glands

decreased insulin secretion ( J:127051 )

• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose