Mouse Genome Informatics
cn1
    Atf6tm1.1Hota/Atf6tm1.1Hota
Tg(Ins2-cre)25Mgn/0

B6.Cg-Atf6tm1.1Hota Tg(Ins2-cre)25Mgn
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• slightly with lower insulin secretion curve in a glucose stimulated insulin secretion assay
• increased cell death in primary islets that is not decreased in the presence of TUDCA

endocrine/exocrine glands
N
• beta cells develop normally
• increased cell death in primary islets that is not decreased in the presence of TUDCA

growth/size/body
N
• mice exhibit normal body weight

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


Mouse Genome Informatics
cn2
    Cdkal1tm1.1Tomik/Cdkal1tm1.1Tomik
Tg(Ins2-cre)25Mgn/0

B6.Cg-Cdkal1tm1.1Tomik Tg(Ins2-cre)25Mgn
Key:
phenotype observed in females
phenotype observed in males
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
cn3
    Slc1a2tm1.1Ncd/Slc1a2tm1.1Ncd
Tg(Ins2-cre)25Mgn/0

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


Mouse Genome Informatics
cn4
    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
phenotype observed in males
N normal phenotype
mortality/aging
N
• expected Mendelian numbers of offspring are detected at weaning; no obvious behavioral or physiological abnormalities are detected

endocrine/exocrine glands
N
• pancreases appears histologically normal compared to controls from 10-23 months

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


Mouse Genome Informatics
cn5
    Ppargtm1.1Gonz/Ppargtm1.1Gonz
Tg(Ins2-cre)25Mgn/0

involves: 129 * C57 * FVB
Key:
phenotype observed in females
phenotype observed in males
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
cn6
    Lipetm2Rze/Lipetm2Rze
Tg(Ins2-cre)25Mgn/?

involves: 129 * C57BL/6 * DBA
Key:
phenotype observed in females
phenotype observed in males
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/body
• significantly increase in overall body fat although body mass remains normal


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
phenotype observed in males
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
phenotype observed in males
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
phenotype observed in males
N normal phenotype
mortality/aging
N
• mice do not exhibit an increase in mortality when fed a high fat diet

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


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

involves: 129P2/OlaHsd * C57BL/6 * CD-1 * DBA
Key:
phenotype observed in females
phenotype observed in males
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/body
• 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
phenotype observed in males
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


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
phenotype observed in males
N normal phenotype
mortality/aging
N
• mice exhibit normal survival

growth/size/body
N
• mice exhibit normal growth


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
phenotype observed in males
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


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

involves: 129P2/OlaHsd * ICR
Key:
phenotype observed in females
phenotype observed in males
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
    Akap5tm1Jsco/Akap5tm1Jsco
Tg(Ins2-cre)25Mgn/0

involves: 129S * C57BL/6 * DBA
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• after intraperitoneal glucose injection in the pancreas
• in fasting mice and after intraperitoneal glucose injection
• despite normal insulin sensitivity

endocrine/exocrine glands
• after intraperitoneal glucose injection in the pancreas


Mouse Genome Informatics
cn16
    Opa1tm1.1Hise/Opa1tm1.2Hise
Tg(Ins2-cre)25Mgn/0

involves: 129S/SvEv * C57BL/6 * DBA * SJL
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
N
• following intraperitoneal insulin injection, mice exhibit normal insulin tolerance
• 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
cn17
    Pdx1tm1Cvw/Pdx1tm4Cvw
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6 * DBA
Key:
phenotype observed in females
phenotype observed in males
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
cn18
    Irs2tm2Mfw/Irs2tm2Mfw
Tg(Ins2-cre)25Mgn/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
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
• 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
cn19
    Irs1tm1Jos/Irs1+
Irs2tm2Mfw/Irs2tm2Mfw
Tg(Ins2-cre)25Mgn/0

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

growth/size/body

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