Mouse Genome Informatics
cn1
    Cdkal1tm1.1Tomik/Cdkal1tm1.1Tomik
Tg(Ins2-cre)25Mgn/0

B6.Cg-Cdkal1tm1.1Tomik Tg(Ins2-cre)25Mgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Endoplasmic reticulum distention in Cdkal1tm1.2Tomik/Cdkal1tm1.2Tomik Tg(Ins2-cre)25Mgn/0 beta cells

endocrine/exocrine glands
• 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
• beta cells exhibit endoplasmic reticulum stress unlike control cells
• beta cells exhibit decreased glucose-stimulated ATP synthesis compared with control cells
• the first-phase of insulin secretion is impaired
• however, the second-phase is normal
• in beta cells 15 minutes after glucose challenge
• following prostprandial stimulation
• in mice fed a high-fat diet

homeostasis/metabolism
• the first-phase of insulin secretion is impaired
• however, the second-phase is normal
• in beta cells 15 minutes after glucose challenge
• following prostprandial stimulation
• in mice fed a high-fat diet
• in fasting and nonfasting mice fed a high-fat diet
• at 5 to 10 weeks of age
• in mice fed a high-fat diet

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:178248


Mouse Genome Informatics
cn2
    Slc1a2tm1.1Ncd/Slc1a2tm1.1Ncd
Tg(Ins2-cre)25Mgn/0

B6.Cg-Slc1a2tm1.1Ncd Tg(Ins2-cre)25Mgn
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice show normal body weights and appearance and show no differences in glucose tolerance


Mouse Genome Informatics
cn3
    Vhltm1Lss/Vhltm1Lss
Tg(Ins2-cre)25Mgn/0

either: (involves: 129X1/SvJ * C57BL/6 * DBA) or (involves: 129X1/SvJ * A/J * C57BL/6 * DBA)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• expected Mendelian numbers of offspring are detected at weaning; no obvious behavioral or physiological abnormalities are detected (J:148174)

endocrine/exocrine glands
N
• pancreases appears histologically normal compared to controls from 10-23 months (J:148174)

Mouse Models of Human Disease
OMIM IDRef(s)
Von Hippel-Lindau Syndrome; VHL 193300 J:148174


Mouse Genome Informatics
cn4
    Ppargtm1.1Gonz/Ppargtm1.1Gonz
Tg(Ins2-cre)25Mgn/0

involves: 129 * C57 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 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


Mouse Genome Informatics
cn5
    Lipetm2Rze/Lipetm2Rze
Tg(Ins2-cre)25Mgn/?

involves: 129 * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 3.5 fold increase in plasma leptin
• impaired insulin and glucagon response to challenge with arginine
• insulin tolerance test suggests a slight improvement in glucose disposal
• 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
• basal plasma glucose levels are significantly elevated at 12 weeks
• 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
• significantly increased beta cell insulin content
• 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
• significantly increase in overall body fat although body mass remains normal

growth/size
• significantly increase in overall body fat although body mass remains normal


Mouse Genome Informatics
cn6
    Akap5tm1Jsco/Akap5tm1Jsco
Tg(Ins2-cre)25Mgn/0

involves: 129 * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• after intraperitoneal glucose injection in the pancreas (J:190017)
• in fasting mice and after intraperitoneal glucose injection (J:190017)
• despite normal insulin sensitivity (J:190017)

endocrine/exocrine glands
• after intraperitoneal glucose injection in the pancreas (J:190017)


Mouse Genome Informatics
cn7
    Nkx6-1tm1Jlr/Nkx6-1tm1.1Msan
Gt(ROSA)26Sortm1(EYFP)Cos/Gt(ROSA)26Sor+
Tg(Ins2-cre)25Mgn/0

involves: 129 * C57BL/6 * DBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• maintenance of beta cell is impaired with conversion to delta cell fate

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


Mouse Genome Informatics
cn8
    Prkcitm1Kido/Prkcitm1Kido
Tg(Ins2-cre)25Mgn/0

involves: 129/Sv * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 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
• 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
• 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


Mouse Genome Informatics
cn9
    Igf1rtm1.1Mhz/Igf1rtm1.1Mhz
Tg(Ins2-cre)25Mgn/0

involves: 129/Sv * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice do not exhibit an increase in mortality when fed a high fat diet (J:121640)

homeostasis/metabolism
• mild on a high fat diet
• on a high fat diet

digestive/alimentary system
N
• when fed a high fat diet mice are capable of manifesting compensatory islet hyperplasia as in wild-type mice (J:121640)


Mouse Genome Informatics
cn10
    Foxa2tm1Khk/Foxa2tm1Khk
Tg(Ins2-cre)25Mgn/0

involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutant animals die between P9 and P12

behavior/neurological

endocrine/exocrine glands
• pancreatic beta cells are present, but have abnormal morphology
• disorganized morphology with non-beta cells present in the core
• beta cells exhibit dysregulated insulin secretion

growth/size
• mutant animals are smaller than controls at P8

homeostasis/metabolism
• beta cells exhibit dysregulated insulin secretion
• described as severe in mutant animals
• level was 5 fold less in mutant mice than in control animals
• the plasma insulin level was very high considering the low glucose levels in mutant animals
• mutant mice have a 2.5-fold higher glycogen content than controls

nervous system


Mouse Genome Informatics
cn11
    Gt(ROSA)26Sortm1(Gck)Ydor/Gt(ROSA)26Sor+
Trp53tm1Brn/Trp53tm1Brn
Tg(Ins2-cre)25Mgn/0

involves: 129P2/OlaHsd * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• some mice die before 3 weeks

homeostasis/metabolism
• slightly less so than in Gt(ROSA)26Sortm1(Gck)Ydor/Gt(ROSA)26Sor+ Tg(Ins2-cre)25Mgn mice

endocrine/exocrine glands
N
• islet architecture and beta cells are preserved in newborns (J:210493)


Mouse Genome Informatics
cn12
    Dlk1tm1.1Jvs/Dlk1+
Tg(Ins2-cre)25Mgn/0

involves: 129P2/OlaHsd * C57BL/6 * DBA * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mice exhibit normal survival (J:194130)

growth/size
N
• mice exhibit normal growth (J:194130)


Mouse Genome Informatics
cn13
    Gt(ROSA)26Sortm1(ptxA)Cgh/Gt(ROSA)26Sor+
Tg(Ins2-cre)25Mgn/0

involves: 129P2/OlaHsd * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• unlike in wild-type mice, glucose and insulin levels are unresponsive to treatment with 3-iodothyronamine
• 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
• 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
N
• despite altered glucose homeostasis, mice exhibit normal pancreatic islet cell size, number, histological appearance and cellular composition (J:130781)


Mouse Genome Informatics
cn14
    Extl3tm1.1Okam/Extl3tm1Okam
Tg(Ins2-cre)25Mgn/0

involves: 129P2/OlaHsd * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• decreased beta-cell area relative to the whole pancreatic area (75%)
• no difference in the islet size
• decreased beta-cell number/total islet cell number ratio (80%) after 2 weeks of age
• beta-cells exist also in the most peripheral region of the islets after 2 weeks of age
• glucagonspositive alpha-cells are scattered in the central region after 2 weeks of age
• islets develop normally at birth
• decreased insulin response to 11.2 mM glucose (47%)
• decreased insulin response to 20 mM KCl (75%)

homeostasis/metabolism
• decreased insulin response to 11.2 mM glucose (47%)
• decreased insulin response to 20 mM KCl (75%)
• decreased plasma insulin levels after glucose loading
• significantly higher blood glucose levels in the glucose tolerance test
• no peripheral insulin resistance in the insulin tolerance test

cellular
• significantly decreased pancreatic islet beta-cell proliferation activity


Mouse Genome Informatics
cn15
    Opa1tm1.1Hise/Opa1tm1.2Hise
Tg(Ins2-cre)25Mgn/0

involves: 129S/SvEv * C57BL/6 * DBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• following intraperitoneal insulin injection, mice exhibit normal insulin tolerance (J:183074)
• in glucose-stimulated beta cells and mice
• however, unstimulated insulin secretion is normal
• under fasted and fed conditions
• in a glucose tolerance test
• following intraperitoneal glucose injection
• in islets in response to glucose stimulation

endocrine/exocrine glands
• decreased beta cell size and density
• newborn mice exhibit increased 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
• in glucose-stimulated beta cells and mice
• however, unstimulated insulin secretion is normal

cellular
• mitochondria in beta cells are highly fragmented, shorter with wider cristae compared to in control cells
• however, volume density of mitochondria is normal
• wider in beta cells compared with control cells
• islets exhibit decreased complex IV activity compared with control cells
• however, activity levels of complex I is normal


Mouse Genome Informatics
cn16
    Pdx1tm1Cvw/Pdx1tm4Cvw
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• proliferation of Pdx1- cells is decreased compared to in wild-type pancreas
• 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
• the number of insulin+ cells decreases as the number of glucagon+ cells increases
• the proliferation of insulin+ cells is decreased
• by one month of age mice are overtly diabetic with decreased insulin immunoreactivity in remaining insulin+ cells
• by one month of age mice are overtly diabetic with increased numbers of somatostatin+ cells
• glucagon+ and somatostatin+ cells are scattered throughout the islet instead of localized to the periphery as in wild-type mice

homeostasis/metabolism
• insulin levels following administration of glucose are lower in males and females compared to wild-type mice
• unlike male mice, females exhibit only mild glucose intolerance compared to wild-type females

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:130389


Mouse Genome Informatics
cn17
    Irs2tm2Mfw/Irs2tm2Mfw
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
pigmentation
• mutants closely resemble agouti mice or mice deficient in Pmoc1 or Mcr4

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

behavior/neurological
• mutants drink 65% more water than wild-type mice
• mutants consume 60% more food than wild-type mice

endocrine/exocrine glands
• 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 fat is increased 2-fold, a disproportionate increase relative to the increase in body weight
• 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
• mutants are 10% longer than wild-type mice

homeostasis/metabolism
• fasting and random-fed glucose levels are elevated
• 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
• serum leptin is increased 2-fold
• glucose intolerance is seen on a normal or low fat diet
• glucose clearance rates were decreased about 50% indicating peripheral insulin resistance

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

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:93415


Mouse Genome Informatics
cn18
    Irs1tm1Jos/Irs1+
Irs2tm2Mfw/Irs2tm2Mfw
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• at 6 months beta cell content is decreased 8-fold

growth/size

homeostasis/metabolism
• diabetes and progressive severe hyperglycemia are seen starting at 4 weeks of age
• severe, progressive hypoinsulinemia is seen

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:93415


Mouse Genome Informatics
cn19
    Irs2tm2Mfw/Irs2tm2Mfw
Tg(Ins2-cre)25Mgn/0
Tg(Ins2-Irs2)13Mfw/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• compound mutants continue to gain excess weight

homeostasis/metabolism
N
• compound mutants do not develop hyperglycemia (J:93415)


Mouse Genome Informatics
cn20
    Tfamtm1Lrsn/Tfamtm1Lrsn
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• decreased blood insulin concentration, onset at 5 week of age
• onset at 27-33 weeks

endocrine/exocrine glands
• normal numbers at 7 weeks, absent at 37 weeks

cellular
• mitochondrial DNA depletion
• respiratory chain dysfunction in pancreatic islets


Mouse Genome Informatics
cn21
    Cacna1ctm3Hfm/Cacna1ctm3Hfm
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 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
• mutants exhibit a slight hyperglycemia under basal and fasted conditions
• 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
• intraperitoneal glucose challenge in fed mice shows impaired glucose tolerance

endocrine/exocrine glands
• calcium currents are reduced in beta cells from mutant mice
• exocytosis in response to the initial depolarizations is reduced in single beta cells
• 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


Mouse Genome Informatics
cn22
    Kif5btm1Njen/Kif5btm1.1Njen
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * C57BL/6 * C57BL/6N * DBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mitochondria cluster in the perinuclear region unlike in wild-type beta cells
• islet cell proliferation is decreased compared to in control mice
• however, the rate of apoptosis is normal
• mice exhibit an increase in insulin vesicles per cell area compared to in wild-type cells
• 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
• in early and slow phase after glucose injection
• after KCl-stimulation of islets
• however, insulin secretion is normal in the absence of glucose stimulation
• progressive increase in random and 16-hour fasting conditions
• in fasting conditions, but not in a random fed state
• 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


Mouse Genome Informatics
cn23
    Kif5btm1Njen/Kif5b+
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * C57BL/6 * C57BL/6N * DBA * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• slight after glucose injection

endocrine/exocrine glands
• slight after glucose injection


Mouse Genome Informatics
cn24
    Nr2f2tm1Vco/Nr2f2tm1Vco
Tg(Ins2-cre)25Mgn/0

involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death occurs before E18.5, possibly due to extrapancreatic cre expression


Mouse Genome Informatics
cn25
    Nr2f2tm1Vco/Nr2f2+
Tg(Ins2-cre)25Mgn/0

involves: 129S2/SvPas * 129X1/SvJ * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• virtually no insulin release in response to glucose challenge
• slightly higher levels of release under basal conditions
• slightly lower plasma glucose levels when fasted
• glucose levels normal when fed
• 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
• glucose intolerant when tested on animals fasted overnight
• very high initial glucose levels after glucose challenge
• levels remain elevated when fed
• decreased free fatty acid levels when fasted

endocrine/exocrine glands
• virtually no insulin release in response to glucose challenge
• slightly higher levels of release under basal conditions


Mouse Genome Informatics
cn26
    Selttm1.1Ics/Selttm1.1Ics
Tg(Ins2-cre)25Mgn/0

involves: 129S2/SvPas * C57BL/6 * C57BL/6J * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• mice exhibit normal insulin sensitivity (J:203279)
• in the pancreas
• after glucose load
• however, basal levels are normal

endocrine/exocrine glands
• increased number of small islets
• however, islet mass is normal
• however, islet mass is normal
• in the pancreas


Mouse Genome Informatics
cn27
    Ptentm1Hwu/Ptentm1Hwu
Rictortm1.1Mgn/Rictortm1.1Mgn
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * 129S6/SvEvTac * BALB/c * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 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
• beta cell mass is about 40% lower than that of single conditional Pten mutants

growth/size

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


Mouse Genome Informatics
cn28
    Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• beta-cell size is increased by 15% compared to controls
• number of proliferating beta-cells is increased by 34% compared to controls
• 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


Mouse Genome Informatics
cn29
    Ghrtm1.1Dlr/Ghrtm1.1Dlr
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * C3H * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

High fat diet-induced obesity causes impaired glucose tolerance and insulin secretion in Ghrtm1.1Dlr/Ghrtm1.1Dlr Tg(Ins2-cre)25Mgn/0 mice

endocrine/exocrine glands
• mice fed a high-fat diet exhibit impaired beta cell hyperplasia compared with similarly treated wild-type mice
• mice fed a high-fat diet exhibit decreased beta cell proliferation compared with wild-type mice
• 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
• 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
• during a glucose tolerance test in mice fed a high-fat diet


Mouse Genome Informatics
cn30
    Irs2tm2Tka/Irs2tm2Tka
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
• the mass of the epididymal fat pad is increased at 12 weeks of age

endocrine/exocrine glands
• 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 weights are significantly greater than controls by 5 weeks of age
• on a regular or high fat diet mutants become obese, however pair fed mutants do not become obese

homeostasis/metabolism
• on a high fat diet but not regular chow fasting glucose levels are significantly elevated
• fasting serum leptin levels are significantly increased and suppression of food intake by exogenous leptin is decreased suggesting leptin resistance
• insulin resistance is seen in mutants without caloric restriction or on a high fat diet


Mouse Genome Informatics
cn31
    Leprdb/Leprdb
Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * C57BL/6 * C57BLKS/J * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• mutants are protected from developing diabetes, and despite severe insulin resistance, mutants remain euglycemic and show normal glucose tolerance (J:170206)
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice
• mutants exhibit a similar degree of insulin resistance as single Leprdb mice

growth/size
• mutants exhibit a similar degree of weight gain as single homozygous Leprdb mice

endocrine/exocrine glands
• islets show similar degrees of hypertrophy and proliferation as those in single homozygous Leprdb mice and do not show a further increase in beta-cell mass compared to the single Leprdb mice
• mutant islets show increased beta-cell function, showing robust insulin secretion after glucose stimulation compared to diminished insulin secretion in single homozygous Leprdb mice


Mouse Genome Informatics
cn32
    Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cellular
• islets are protected from oxidative stress

endocrine/exocrine glands
• increase in beta cell size
• beta-cells maintain intact response to DNA-damaging stimuli unlike controls
• 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
• number of insulin-producing cells is increased in islets
• 1.5-fold increase in islet numbers
• 2-fold increase in islet size
• decrease in apoptotic rate during pancreas remodeling at P17
• however, pancreas exhibits normal islet functions
• increase in beta-cell proliferation at E17.5
• 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
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 (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, however mice respond normally to a glucose challenge
• mutants are protected from high-fat diet-induced diabetes, remaining euglycemic and showing improved glucose tolerance than controls on a high-fat diet
• increase in peripheral insulin sensitivity
• mice are protected from STZ-induced beta-cell injury and diabetes

growth/size


Mouse Genome Informatics
cn33
    Insrtm1Khn/Insrtm1Khn
Tg(Alb-cre)21Mgn/0
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 82% of mice die by 6 weeks of age with some mice surviving a few weeks longer

homeostasis/metabolism
• mice develop hypoglycemia at 2 weeks of age that rapidly worsens by 6 weeks of age
• mice exhibit high fasting glucose serum levels

endocrine/exocrine glands

renal/urinary system
• during terminal stages

behavior/neurological
• during terminal stages

digestive/alimentary system
N
• unlike mice null for Insr in beta cells mice, islet cell mass is not increased despite similar levels of elevated insulin levels (J:121640)

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


Mouse Genome Informatics
cn34
    Insrtm1Khn/Insrtm1Khn
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• when fed a high fat diet, 30% of mice die by 16 weeks
• some mice die due to severe hyperglycemia

homeostasis/metabolism
• mice exhibit an increase in serum glucose level on a regular diet and a severe increase when fed a high fat diet
• 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
• mice exhibit decreased beta cell mass when fed a normal or high fat diet


Mouse Genome Informatics
cn35
    Rictortm1.1Mgn/Rictortm1.1Mgn
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * BALB/c * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 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
• pancreatic insulin content is about 50% less than controls
• number of proliferating beta-cells is decreased by 26% compared to controls
• islets have approximately 70% lower insulin secretion in response to glucose than controls
• however, insulin sensitivity is normal

homeostasis/metabolism
• total glucose excursion is higher compared to controls
• islets have approximately 70% lower insulin secretion in response to glucose than controls
• however, insulin sensitivity is normal
• mutants exhibit hyperglycemia beginning at 12 weeks of age
• 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


Mouse Genome Informatics
cn36
    Chrm3tm2Jwe/Chrm3tm2Jwe
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• insulin release following treatment with oxotremorine-M is reduced 50% compared to from wild-type islet cells
• however, total insulin content is normal
• 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
• insulin release following treatment with oxotremorine-M is reduced 50% compared to from wild-type islet cells
• however, total insulin content is normal


Mouse Genome Informatics
cn37
    Neurog3tm1(cre/ERT)Ggu/Neurog3tm1(cre/ERT)Ggu
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 13 weeks after birth


Mouse Genome Informatics
cn38
    Neurog3tm1(cre/ERT)Ggu/Neurog3tm1.1(cre/ERT)Ggu
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• at 6 weeks compared to in Neurog3tm1(cre/ESR1)Ggu/Neurog3tm1.1(cre/ESR1)Ggu mice


Mouse Genome Informatics
cn39
    Stat5a/Stat5btm2Mam/Stat5a/Stat5btm2Mam
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• elevated adipose tissue mass of female mice
• normal lean mass
• mild obesity
• weigh on the average 20% more than their control littermates by 9 months of age

adipose tissue
• elevated adipose tissue mass of female mice
• normal lean mass

homeostasis/metabolism
• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose
• slightly elevated serum glucose levels at 7 months of age
• higher serum leptin levels at 7 months of age
• normal serum insulin levels
• higher serum free fatty acids levels at 7 months of age
• 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
• disrupted architecture of islets as evidenced by the migration of glucagon-expressing alpha-cells into the central region of the islets
• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose


Mouse Genome Informatics
cn40
    Stat5a/Stat5btm2Mam/Stat5a/Stat5btm2Mam
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• elevated adipose tissue mass of female mice
• normal lean mass
• mild obesity
• weigh on the average 20% more than their control littermates by 9 months of age

adipose tissue
• elevated adipose tissue mass of female mice
• normal lean mass

homeostasis/metabolism
• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose
• slightly elevated serum glucose levels at 7 months of age
• higher serum leptin levels at 7 months of age
• normal serum insulin levels
• higher serum free fatty acids levels at 7 months of age
• 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
• disrupted architecture of islets as evidenced by the migration of glucagon-expressing alpha-cells into the central region of the islets
• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose


Mouse Genome Informatics
cn41
    Gcktm1.1Mgn/Gcktm1.1Mgn
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• more than 80% neonatal mortality as a result of severe hyperglycemia

homeostasis/metabolism
• highly variable but increased blood glucose concentrations
• decreased by about 70%
• diminished hepatic glycogen

liver/biliary system

Mouse Models of Human Disease
OMIM IDRef(s)
Maturity-Onset Diabetes of the Young, Type 2; MODY2 125851 J:51826


Mouse Genome Informatics
cn42
    Gcktm1.1Mgn/Gck+
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 70% decrease in insulin secretion during hyperglycemic clamp studies
• blood glucose concentration is increased by about 50% compared to heterozygous Gcktm1.1Mgn mice
• under fasting conditions, have a 25% increase in blood glucose concentration, without differences in basal insulin concentration
• glucose turnover and glucose infusion rates during hyperglycemic clamp are reduced by about 60 and 70%, respectively
• net glycogen synthesis in liver is reduced by about 50% during hyperglycemic clamp studies

endocrine/exocrine glands
• 70% decrease in insulin secretion during hyperglycemic clamp studies

Mouse Models of Human Disease
OMIM IDRef(s)
Maturity-Onset Diabetes of the Young, Type 2; MODY2 125851 J:51826


Mouse Genome Informatics
cn43
    Men1tm1Ctre/Men1tm1Ctre
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• 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

homeostasis/metabolism
• fasting blood glucose levels are decreased
• fasting serum insulin levels are increased

tumorigenesis
• 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


Mouse Genome Informatics
cn44
    Men1tm1Ctre/Men1+
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• heterozygous mutants develop islet tumors later than homozygous mutants


Mouse Genome Informatics
cn45
    Irs2tm1With/Irs2tm1With
Tg(Ins2-cre)25Mgn/0

involves: 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 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
• fasting hyperinsulinemia is seen at 12 weeks and 6 months of age
• at 12 weeks, but not 5 weeks, of age leptin levels are significantly elevated
• defective glucose disposal is seen at 12 weeks and 6 months of age

endocrine/exocrine glands
• 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 weight is increased by 4 - 5 weeks of age and 20% more by 12 weeks of age compared to controls

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


Mouse Genome Informatics
cn46
    Men1tm1Gfk/Men1tm1Gfk
Tg(Ins2-cre)25Mgn/0

involves: 129T2/SvEms * C57BL/6 * C57BL/6J * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• by 12 months of age, 15 mice develop adenomas in the anterior pituitary gland that are prolactin positive
• 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

endocrine/exocrine glands
• prominent in multiple islets consisting of beta cell hyperplasia


Mouse Genome Informatics
cn47
    Hnf4atm1.1Gonz/Hnf4atm1.1Gonz
Tg(Ins2-cre)25Mgn/0

involves: 129X1/SvJ * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 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
• 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
• KATP activity is reduced in knockouts; decreased response leads to impaired insulin secretion

Mouse Models of Human Disease
OMIM IDRef(s)
Maturity-Onset Diabetes of the Young, Type 1; MODY1 125850 J:108652


Mouse Genome Informatics
cn48
    Fasntm1Sem/Fasntm1Sem
Tg(Ins2-cre)25Mgn/?

involves: 129X1/SvJ * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size
• 16-20 week old mice have about half the amount of adipose tissues as littermate controls
• weight differences are due to decreased amounts of adipose tissue
• mice weigh less than littermate controls starting at 7 weeks of age for males and 13 weeks of age for females

homeostasis/metabolism
• glucose levels are about 20% higher than in wild-type mice fed the same amount of food
• levels are about 60% higher than in wild-type mice fed the same amount of food
• levels are about 55% higher than in wild-type mice fed the same amount of food
• is observed under both fed and fasted conditions
• increase in oxygen consumption is 20% higher than controls following a 24 hour fast
• 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
• levels are about 41% lower than in wild-type mice fed the same amount of food

behavior/neurological
• freely fed mice consume 17% less food than controls
• mice consume less than controls 4 hours and 24 hours after food is reintroduced after fasting
• 20% to 300% increase in locomoter activity depending on timeframe and measuring methods that are used

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

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

endocrine/exocrine glands
• defects in fatty acid synthesis


Mouse Genome Informatics
cn49
    Slc30a8tm1.1Htwt/Slc30a8tm1.1Htwt
Tg(Ins2-cre)25Mgn/0

involves: C57BL/6 * CBA/JNCrlj * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
liver/biliary system
N
• mice exhibit normal liver function (J:204003)

homeostasis/metabolism
N
• mice exhibit normal insulin tolerance, glucagon secretion and metabolic response to a high-fat diet (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
• mildly in mice fed chow
• increased insulin clearance after glucose challenge
• proinsulin to insulin ratio is slightly higher than in wild-type mice
• low zinc content in beta cell islets

endocrine/exocrine glands
• 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
• 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


Mouse Genome Informatics
cn50
    Prkar2btm3Gsm/Prkar2btm2Gsm
Tg(Ins2-cre)25Mgn/0

involves: C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• hyperactivity phenotype is reduced (J:196157)

growth/size
N
• body weight similar to controls (J:196157)
• lean body mass is similar to controls (J:196157)

adipose tissue
N
• adiposity similar to controls (J:196157)

homeostasis/metabolism
N
• serum leptin levels similar to controls (J:196157)


Mouse Genome Informatics
cn51
    Gt(ROSA)26Sortm1(Gck)Ydor/Gt(ROSA)26Sor+
Tg(Ins2-cre)25Mgn/0

involves: C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most mice die during the first week of life

homeostasis/metabolism
• at birth

endocrine/exocrine glands
• reduced beta cell area at E16.5 and birth


Mouse Genome Informatics
cn52
    Fastm1Vbo/Fastm1Vbo
Tg(Ins2-cre)25Mgn/0
Tg(Ins2-HA)165Bri/0
Tg(Tcra/Tcrb)1Vbo/0

Not Specified
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• autoimmune diabetes developed with accelerated kinetics

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Insulin-Dependent; IDDM 222100 J:85985


Mouse Genome Informatics
cx53
    Bcl2l1tm1.1Mam/Bcl2l1tm1.1Mam
Tg(Ins2-cre)25Mgn/0
Tg(RIP1-Tag)2Dh/0

involves: 129S6/SvEvTac * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 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
OMIM IDRef(s)
Pancreatic Cancer 260350 J:146436


Mouse Genome Informatics
tg54
    Tg(Ins2-cre)25Mgn/0
either: (B6.Cg-Tg(Ins2-cre)25Mgn/J) or (involves: 129 * C57BL/6 * DBA/2)
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• 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
• 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
• 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
• 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


Mouse Genome Informatics
tg55
    Tg(Ins2-cre)25Mgn/0
involves: C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose
• glucose intolerance as early as 6 weeks of age

endocrine/exocrine glands
• reduced insulin secretion from isolated islets upon challenge with 16.7 mM of glucose