Phenotypes associated with this allele

• Allele Symbol: Ins2⁺
• Allele Name: wild type
• Allele ID: MGI:2431236
• Summary: 18 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Ins2^em#Arak/Ins2^+	C.129-Rag2^tm1Fwa Ins2^em#Arak Jak3^tm1Tks/Arak	MGI:6478875
ht2	Ins2^C95S/Ins2^+	C3HeB/FeJ-Ins2^C95S	MGI:3714127
ht3	Ins2^Akita/Ins2^+	C57BL/6-Ins2^Akita	MGI:3583904
ht4	Ins2^Akita/Ins2^+	C57BL/6-Ins2^Akita/J	MGI:3583907
ht5	Ins2^Akita/Ins2^+	C.B6N-Ins2^Akita	MGI:5508895
ht6	Ins2^tm1Delt/Ins2^+	involves: 129S2/SvPas * Black Swiss	MGI:3521710
ht7	Ins2^Akita/Ins2^+	involves: C3H * C57BL/6NJcl * C57BL/6NSlc	MGI:3583905
ht8	Ins2^Akita/Ins2^+	involves: C57BL/6NSlc	MGI:5510482
cx9	Bdkrb2^tm1Jfh/Bdkrb2^tm1Jfh Ins2^Akita/Ins2^+	B6.Cg-Ins2^Akita Bdkrb2^tm1Jfh	MGI:3626074
cx10	Ins2^Akita/Ins2^+ Or12d17^em1Cya/Or12d17^em1Cya	C57BL/6-Ins2^Akita Or12d17^em1Cya	MGI:7664100
cx11	Ins1^tm1Jja/Ins1^tm1Jja Ins2^tm1Jja/Ins2^+	involves: 129S2/SvPas * C57BL/6	MGI:3640381
cx12	Ero1b^Gt(P077G11)Wrst/Ero1b^+ Ins2^Akita/Ins2^+	involves: 129S2/SvPas * C57BL/6NSlc	MGI:4441480
cx13	Gast^tm1(INS)Ez/Gast^+ Ins2^Akita/Ins2^+	involves: 129S4/SvJae * C57BL/6NSlc	MGI:3583903
cx14	Dbm3^C57BL/6J/? Ins2^Akita/Ins2^+	involves: A/J * C57BL/6J * C57BL/6NSlc	MGI:3664326
cx15	Dbm1^A/J/Dbm1^A/J Ins2^Akita/Ins2^+	involves: A/J * C57BL/6J * C57BL/6NSlc	MGI:3664324
cx16	Dbm4^C57BL/6J/? Ins2^Akita/Ins2^+	involves: A/J * C57BL/6J * C57BL/6NSlc	MGI:3664327
cx17	Ins2^Akita/Ins2^+ Rnf213^tm1.1Akoi/Rnf213^tm1.1Akoi	involves: C57BL/6N * C57BL/6NSlc	MGI:5510483
cx18	Ins2^Akita/Ins2^+ Prf1^tm1Sdz/Prf1^tm1Sdz Rag1^tm1Mom/Rag1^tm1Mom	NOD.Cg-Rag1^tm1Mom Ins2^Akita Prf1^tm1Sdz	MGI:3817777

Genotype
MGI:6478875

ht1

• Allelic Composition: Ins2^em#Arak/Ins2⁺
• Genetic Background: C.129-Rag2^tm1Fwa Ins2^em#Arak Jak3^tm1Tks/Arak

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

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:294041 )

• islets show a reduction in insulin protein level at 3 weeks of age, which is further decreased at 7 weeks of age

abnormal pancreatic beta cell morphology ( J:294041 )

• islet insulin-positive beta-cell area becomes significantly smaller at 10 weeks of age

• islet beta cells show a reduction in number and size of insulin granules in 5-week old mice

• cores of insulin granules are less electron-dense than in wild-type mice, indicating immature beta cells

• endoplasmic reticulum shows dilated vesicular morphologies in beta cells

• reduction in insulin granule area in proportion to the beta cells area

small pancreatic islets ( J:294041 )

• islet size becomes significantly smaller at 10 weeks of age

• islet mass is decreased in 7-week old mice

• mice transplanted with insulin implants show no difference in islet size from untreated mice

homeostasis/metabolism

abnormal homeostasis ( J:294041 )

• mice exhibit non-obese permanent neonatal diabetes

hyperglycemia ( J:294041 )

• hyperglycemia in males and females from 4 weeks of age and on

• females show milder hyperglycemia than males

• mice transplanted with insulin implants show normalized hyperglycemia that is sustained for a month; removal of transplant results in recurrence of hyperglycemia

impaired glucose tolerance ( J:294041 )

• mice are glucose intolerant

• however, males how normal insulin tolerance at 4- and 10-weeks of age

renal/urinary system

polyuria ( J:294041 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
neonatal diabetes mellitus		DOID:11717		J:294041

Genotype
MGI:3714127

ht2

• Allelic Composition: Ins2^C95S/Ins2⁺
• Genetic Background: C3HeB/FeJ-Ins2^C95S

homeostasis/metabolism

decreased insulin secretion ( J:122098 )

• pancreatic insulin levels are reduced

increased circulating glucose level ( J:122098 )

• 48% of males and 41% of females are considered diabetic (i.e. showing glucosuria or exhibiting blood glucose levels greater than 160mg/dl for females and 190mg/dl for males)

• at 1, 3, 6 months fasted and 1.5 hours postprandial blood glucose levels are elevated in males and females

• however, blood glucose levels at 3 weeks are normal

hyperglycemia ( J:122098 , J:137483 )

• in 66% of mice (J:137483)

decreased circulating insulin level ( J:122098 )

• at 10 minutes after glucose challenge, serum insulin levels are reduced

increased urine glucose level ( J:122098 )

• 48% of males and 41% of females are considered diabetic (i.e. showing glucosuria or exhibiting blood glucose levels greater than 160mg/dl for females and 190mg/dl for males)

insulin resistance ( J:122098 )

• homeostasis model assessment (HOMA) of insulin resistance is higher in 1 month old females and in 3 and 6 month old males

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:122098 )

• islet volume is significantly lower due to a decrease in beta cell volume while alpha, delta and PP cell volumes are significantly higher

• however, pancreatic volume is normal

increased pancreatic alpha cell number ( J:122098 )

• alpha cell numbers are increased

abnormal pancreatic beta cell morphology ( J:122098 )

• while no apoptotic bodies are observed rough endoplasmic reticulum is disorganized and mitochondria are swollen

• insulin secretory granules are almost missing and remaining granules are small

decreased pancreatic beta cell number ( J:122098 )

• insulin secretory granules are almost missing

disorganized pancreatic islets ( J:122098 )

• alpha cells are dispersed over the islet profile unlike in wild-type mice

abnormal pancreatic beta cell physiology ( J:122098 )

• homeostasis model assessment (HOMA) beta-cell index is reduced

decreased insulin secretion ( J:122098 )

• pancreatic insulin levels are reduced

immune system

increased susceptibility to autoimmune diabetes ( J:122098 )

• 48% of males and 41% of females are considered diabetic (i.e. showing glucosuria or exhibiting blood glucose levels greater than 160mg/dl for females and 190mg/dl for males)

renal/urinary system

increased urine glucose level ( J:122098 )

• 48% of males and 41% of females are considered diabetic (i.e. showing glucosuria or exhibiting blood glucose levels greater than 160mg/dl for females and 190mg/dl for males)

growth/size/body

decreased body weight ( J:122098 )

• fasted body weight at 3 and 6 months of ages for males is significantly lower than sex-matched wild-type mice

Genotype
MGI:3583904

ht3

• Allelic Composition: Ins2^Akita/Ins2⁺
• Genetic Background: C57BL/6-Ins2^Akita

mortality/aging

premature death ( J:108948 , J:40063 )

• mice have much shorter lifespan than wild-type; 909 days (wt) vs 373 days (mutant) (J:108948)

♂ • 50% survival time in males is reduced to 305 days but survival time is not reduced for females through 370 days of age (J:40063)

homeostasis/metabolism

decreased insulin secretion ( J:47883 , J:40063 )

• the pancreatic ratio of insulin to glucagon is decreased to 0.42 and 0.54 at birth and 14 days of age, respectively compared to 1.17 and 1.11 in wild-type mice (J:47883)

• hyposecretion of insulin is seen; however, islet area is not reduced (J:40063)

hyperglycemia ( J:125256 , J:40063 )

• develops soon after weaning and is more severe in males (J:40063)

♂ • blood glucose in fed 7-8 week old males measures 544+/-11 mg/dl (J:125256)

decreased circulating insulin level ( J:40063 )

• insulin levels are decreased in the blood and pancreas

impaired glucose tolerance ( J:40063 )

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:47883 )

• density of beta cells is decreased at 14 days of age

• beta cells have increased amounts of endoplasmic reticulum and Golgi complexes, more and enlarged mitochondria, and partial degranulation

degranulated pancreatic beta cells ( J:47883 )

• partial degranulation

abnormal Leydig cell morphology ( J:108948 )

♂ • mutant males display some pigmented vacuoles in Leydig cells in the testes, but to a lesser extent than in double mutant males at 12 months of age

decreased insulin secretion ( J:47883 , J:40063 )

• the pancreatic ratio of insulin to glucagon is decreased to 0.42 and 0.54 at birth and 14 days of age, respectively compared to 1.17 and 1.11 in wild-type mice (J:47883)

• hyposecretion of insulin is seen; however, islet area is not reduced (J:40063)

renal/urinary system

hydronephrosis ( J:40063 )

• seen in all diabetic males but only 5 of 20 diabetic females

polyuria ( J:40063 )

• develops soon after weaning and is more severe in males

behavior/neurological

increased fluid intake ( J:125256 )

♂ • 7-8 week old males consume 7 fold more water as compared to controls (33.28 ml/day v. 4.68 ml/day)

polydipsia ( J:40063 )

• develops soon after weaning and is more severe in males

polyphagia ( J:125256 )

♂ • 7-8 week old males consume 2 fold more food as compared to controls (8.16 g/day v. 4.48 g/day)

increased anxiety-related response ( J:125256 )

♂ • 7-8 week old males exhibit greater anxiety behavior in elevated plus maze

♂ • total number and total time of entries in the open arms is significantly decreased as compared to controls

akinesia ( J:125256 )

♂ • 7-8 week old males exhibit increased immobility time as measured in open field test

decreased locomotor activity ( J:125256 )

♂ • 7-8 week old males exhibit decreased locomotor activity as measured in open field test

♂ • number of total entries in elevated plus maze is decreased in 7-8 week old males as compared to controls

growth/size/body

decreased body weight ( J:125256 )

♂ • 7-8 week old males exhibit decreased weight as compared to controls (24g v. 26g)

postnatal growth retardation ( J:40063 )

• weight gain is normal through 18 weeks of age but then no further weight gain is seen and by 30 weeks weight loss is observed

adipose tissue

decreased subcutaneous adipose tissue amount ( J:108948 )

• mutants have almost no subcutaneous fat

cellular

abnormal mitochondrial morphology ( J:108948 )

• mutant mice show greater mitochondrial damage than wild-type or Bdkrb2-deficient mice at 12 months of age

reproductive system

abnormal Leydig cell morphology ( J:108948 )

♂ • mutant males display some pigmented vacuoles in Leydig cells in the testes, but to a lesser extent than in double mutant males at 12 months of age

skeleton

kyphosis ( J:108948 )

• diabetic mice display kyphosis but to a lesser extent than double mutant mice

decreased bone mineral density ( J:108948 )

• mutants have significantly reduced bone density compared to wild-type or Bdkrb2-deficient mice

integument

decreased subcutaneous adipose tissue amount ( J:108948 )

• mutants have almost no subcutaneous fat

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young		DOID:0050524	OMIM:PS125850	J:40063

Genotype
MGI:3583907

ht4

• Allelic Composition: Ins2^Akita/Ins2⁺
• Genetic Background: C57BL/6-Ins2^Akita/J

homeostasis/metabolism

hyperglycemia ( J:76224 , J:99412 )

• heterozygous males and females are hyperglycemic by 6 weeks of age (plasma glucose - 325 mg/dL); at 12 and 18 weeks of age, plasma glucose levels in males have appproximately doubled (645 mg/dL and 666 mg/dL) while levels in female mutants have increased much less (341 and 298 mg/dL respectively) (J:76224)

decreased circulating insulin level ( J:321591 )

• mice show decreased glucose-induced plasma insulin levels during glucose tolerance testing

increased energy expenditure ( J:321591 )

• mice exhibit increased energy expenditure in the dark photo-period at 2 to 3 months of age

decreased respiratory quotient ( J:321591 )

• mice present reduced respiratory quotient values at 2 to 3 months of age

impaired glucose tolerance ( J:321591 )

• mice exhibit increased blood glucose levels after glucose injection in glucose tolerance tests

• treatment with a pepducin based on Or12d17 sequence, o109-i2-2, significantly ameliorates the glucose metabolism disorder seen in mutants

increased insulin sensitivity ( J:76224 )

• diabetic males that are hyperglycemic (plasma glucose - ~660 mg/dL) at 12 weeks show a return to euglycemia one hour after receiving 1 unit of insulin, demonstrating insulin sensitivity

immune system

abnormal microglial cell morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

increased leukocyte cell number ( J:99412 )

• after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased

abnormal response to transplant ( J:76224 )

• hyperglycemic male mice transplanted with pancreatic islets from wild-type B6 males become euglycemic in one week after transplant and remain euglycemic until removal of the graft (8 weeks); male mice receiving an allogeneic transplant of BALB/c wild-type islets initially become euglycemic but revert to hyperglycemia because of rejection of the graft

cardiovascular system

abnormal retina vasculature morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina

increased vascular permeability ( J:99412 )

• vascular permeability is increased in the retina

growth/size/body

decreased body weight ( J:99412 , J:321591 )

• at death heterozygous males weigh significantly less than wild-type males (J:99412)

• body weight is decreased at 2 to 3 months of age (J:321591)

nervous system

abnormal astrocyte morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, astrocytes close to large caliber superficial blood vessels in the retina have short projections that do not conjoin with the vessel

abnormal microglial cell morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

vision/eye

abnormal retina vasculature morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, a modest increase in the number of acellular capillaries is seen in the retina

increased retina apoptosis ( J:99412 )

• after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen

abnormal retina neuronal layer morphology ( J:99412 )

• after 22 weeks of hyperglycemia, in the peripheral regions the inner nuclear layer and inner plexiform layer thickness are reduced by 15.6% and 27%, respectively, and in the central region the thickness of the inner plexiform layer is reduced by 16.7%

abnormal retina ganglion layer morphology ( J:99412 )

• after 22 weeks of hyperglycemia, the number of nuclei in the retinal ganglion cell layer is reduced by 23.4%

hematopoietic system

abnormal microglial cell morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

increased leukocyte cell number ( J:99412 )

• after 31-36 weeks of hyperglycemia, the number of leukocytes per retina is increased

cellular

abnormal astrocyte morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, astrocytes close to large caliber superficial blood vessels in the retina have short projections that do not conjoin with the vessel

abnormal microglial cell morphology ( J:99412 )

• after 31-36 weeks of hyperglycemia, retinal microglia have a reactive morphology

increased retina apoptosis ( J:99412 )

• after 31-36 weeks of hyperglycemia, significantly more caspase-3 positive cells are seen

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:321591 )

• mice exhibit a large reduction in insulin content of islets

• population of CD11c+ macrophages in islets is increased by about 3-fold compared to wild-type mice

decreased pancreatic beta cell number ( J:321591 )

• marker analysis indicates that mice show reduced pancreatic beta cells in islets

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young		DOID:0050524	OMIM:PS125850	J:99412

Genotype
MGI:5508895

ht5

• Allelic Composition: Ins2^Akita/Ins2⁺
• Genetic Background: C.B6N-Ins2^Akita

homeostasis/metabolism

albuminuria ( J:198186 )

• 3-fold increase in albumin-to-creatine ratio at 4 months of age, however albuminuria does not persist at 6 months of age

renal/urinary system

albuminuria ( J:198186 )

• 3-fold increase in albumin-to-creatine ratio at 4 months of age, however albuminuria does not persist at 6 months of age

expanded mesangial matrix ( J:198186 )

• mesangial matrix expansion is seen at 4 months of age

glomerulosclerosis ( J:198186 )

• same degree of glomerular injury as in homozygotes at 6 months of age

increased renal glomerular filtration rate ( J:198186 )

• glomerular filtration rate is increased at 6 months of age

Genotype
MGI:3521710

ht6

• Allelic Composition: Ins2^tm1Delt/Ins2⁺
• Genetic Background: involves: 129S2/SvPas * Black Swiss

mortality/aging

postnatal lethality, complete penetrance ( J:94589 )

• heterozygotes die around P2 with severe diabetes mellitus and ketoacidosis

endocrine/exocrine glands

decreased pancreatic alpha cell number ( J:94589 )

• at E12.5 there is an 85% decrease in the alpha cell population however the number of alpha cells is normal in neonates

absent pancreatic beta cells ( J:94589 )

• no beta cells are detected in the pancreas

small pancreatic islets ( J:94589 )

• islet size is reduced as a result of absence of beta cells

• the numbers of alpha, delta, and pancreatic polypetide cells are normal in newborn mutants

growth/size/body

postnatal growth retardation ( J:94589 )

homeostasis/metabolism

increased circulating ketone body level ( J:94589 )

• ketone bodies are detected the day after onset of suckling

dehydration ( J:94589 )

increased urine glucose level ( J:94589 )

• detected a few hours after pups begin suckiling

liver/biliary system

hepatic steatosis ( J:94589 )

renal/urinary system

increased urine glucose level ( J:94589 )

• detected a few hours after pups begin suckiling

Genotype
MGI:3583905

ht7

• Allelic Composition: Ins2^Akita/Ins2⁺
• Genetic Background: involves: C3H * C57BL/6NJcl * C57BL/6NSlc

homeostasis/metabolism

hyperglycemia ( J:40063 )

• progressive increase in morning blood glucose level is seen

impaired glucose tolerance ( J:40063 )

Genotype
MGI:5510482

ht8

• Allelic Composition: Ins2^Akita/Ins2⁺
• Genetic Background: involves: C57BL/6NSlc

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:200802 )

N • mice exhibit normal insulin sensitivity

decreased insulin secretion ( J:200802 )

• decreased total pancreatic insulin and prolinsulin content

increased circulating glucose level ( J:200802 )

decreased circulating leptin level ( J:200802 )

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:200802 )

• beta cells contain a small number of secretory granules, a tubulovesicular structure comprised of enlarged endoplasmic reticulum, and swelling or disruption of mitochondria

decreased insulin secretion ( J:200802 )

• decreased total pancreatic insulin and prolinsulin content

growth/size/body

decreased body weight ( J:200802 )

behavior/neurological

increased food intake ( J:200802 )

Genotype
MGI:3626074

cx9

• Allelic Composition: Bdkrb2^tm1Jfh/Bdkrb2^tm1Jfh; Ins2^Akita/Ins2⁺
• Genetic Background: B6.Cg-Ins2^Akita Bdkrb2^tm1Jfh

mortality/aging

premature death ( J:108948 )

• mice have much shorter lifespan than wild-type; 909 days (wt) vs 246 days (mutant)

cellular

abnormal spermatogonia morphology ( J:108948 )

♂ • in double mutant males, severe loss of spermatogonia is observed and atrophy of spermatic cords is prevalent at 12 months of age

abnormal mitochondrial chromosome morphology ( J:108948 )

• mutants display increased mitochondrial DNA damage compared to single mutants or wild-type mice at 12 months of age

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:108948 )

♂ • double mutants have an increased frequency of apoptotic cells in the seminiferous tubules at 12 months of age

abnormal Leydig cell morphology ( J:108948 )

♂ • double mutant males display numerous pigmented vacuoles in Leydig cells in the testes at 12 months of age

reproductive system

abnormal spermatogonia morphology ( J:108948 )

♂ • in double mutant males, severe loss of spermatogonia is observed and atrophy of spermatic cords is prevalent at 12 months of age

abnormal seminiferous tubule morphology ( J:108948 )

♂ • double mutants have an increased frequency of apoptotic cells in the seminiferous tubules at 12 months of age

abnormal Leydig cell morphology ( J:108948 )

♂ • double mutant males display numerous pigmented vacuoles in Leydig cells in the testes at 12 months of age

abnormal spermatic cord morphology ( J:108948 )

♂ • double mutant males show atrophy of the spermatic cords at 12 months of age

digestive/alimentary system

abnormal intestinal epithelium morphology ( J:108948 )

• intestinal villi in mutants have a greater frequency of apoptotic cells

adipose tissue

decreased subcutaneous adipose tissue amount ( J:108948 )

• mutants have almost no subcutaneous fat

skeleton

kyphosis ( J:108948 )

• double mutants exhibit marked kyphosis

decreased bone mineral density ( J:108948 )

• double mutants have significantly reduced bone density compared to wild-type or single mutant mice

integument

decreased subcutaneous adipose tissue amount ( J:108948 )

• mutants have almost no subcutaneous fat

alopecia ( J:108948 )

• most mutants show significant alopecia by 12 months of age

Genotype
MGI:7664100

cx10

• Allelic Composition: Ins2^Akita/Ins2⁺; Or12d17^em1Cya/Or12d17^em1Cya
• Genetic Background: C57BL/6-Ins2^Akita Or12d17^em1Cya

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:321591 )

N • islets show increased expression of pancreatic beta cell markers in islets than that seen in Ins2^Akita mice, indicating rescue of the reduced pancreatic beta cells in islets

abnormal pancreatic islet morphology ( J:321591 )

• mice show partial rescue of the decreased insulin content in islets seen in Ins2^Akita mice but insulin content is still lower than in wild-type mice

• mice show partial rescue of the increased CD11c+ macrophages in islets of Ins2^Akita mice

growth/size/body

growth/size/body region phenotype ( J:321591 )

N • mice show rescue of the decreased body weight seen in heterozygous Ins2^Akita mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:321591 )

N • mice show reversal of the increased energy expenditure and reduced respiratory quotient seen in the dark photo-period of heterozygous Ins2^Akita mice

decreased circulating insulin level ( J:321591 )

• mice show improved glucose-induced plasma insulin levels at 8 weeks of age compared to heterozygous Ins2^Akita mice but not fully to wild-type levels

impaired glucose tolerance ( J:321591 )

• mice show markedly improved glucose tolerance at 8 weeks of age compared to heterozygous Ins2^Akita mice but not fully to wild-type levels

Genotype
MGI:3640381

cx11

• Allelic Composition: Ins1^tm1Jja/Ins1^tm1Jja; Ins2^tm1Jja/Ins2⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

endocrine/exocrine glands

increased pancreatic alpha cell mass ( J:106827 )

• total alpha cell mass is increased compared to wild-type (68 ug vs 48 ug w.t.)

Genotype
MGI:4441480

cx12

• Allelic Composition: Ero1b^{Gt(P077G11)Wrst}/Ero1b⁺; Ins2^Akita/Ins2⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6NSlc

homeostasis/metabolism

decreased insulin secretion ( J:158805 )

• in the pancreas

increased circulating glucose level ( J:158805 )

• plasma glucose levels are higher than in Ins2^Akita heterozygotes

impaired glucose tolerance ( J:158805 )

• glucose intolerance is worse than in Ins2^Akita heterozygotes

endocrine/exocrine glands

small pancreatic islets ( J:158805 )

decreased insulin secretion ( J:158805 )

• in the pancreas

Genotype
MGI:3583903

cx13

• Allelic Composition: Gast^tm1(INS)Ez/Gast⁺; Ins2^Akita/Ins2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6NSlc

mortality/aging

mortality/aging ( J:99270 )

N • double heterozygotes live over 13 months compared to Ins2^Akita single heterozygotes which have a median survival time of 10.3 months

homeostasis/metabolism

abnormal circulating glucose level ( J:99270 )

• a significant decrease in fasting hyperglycemia is seen in double heterozygotes compared to Ins2^Akita single heterozygotes

Genotype
MGI:3664326

cx14

• Allelic Composition: Dbm3^C57BL/6J/?; Ins2^Akita/Ins2⁺
• Genetic Background: involves: A/J * C57BL/6J * C57BL/6NSlc

homeostasis/metabolism

abnormal circulating glucose level ( J:112869 )

• increased fasting plasma glucose concentration in males

• increased plasma glucose at 30, 60, and 120 minutes of the intraperitoneal glucose tolerance test in males

Genotype
MGI:3664324

cx15

• Allelic Composition: Dbm1^A/J/Dbm1^A/J; Ins2^Akita/Ins2⁺
• Genetic Background: involves: A/J * C57BL/6J * C57BL/6NSlc

homeostasis/metabolism

increased circulating glucose level ( J:112869 )

• increased fasting plasma glucose concentration in males

• increased plasma glucose at all time points of the intraperitoneal glucose tolerance test in males

increased circulating insulin level ( J:112869 )

• increased plasma insulin concentration in males

growth/size/body

increased body weight ( J:112869 )

• increased body weight in males

Genotype
MGI:3664327

cx16

• Allelic Composition: Dbm4^C57BL/6J/?; Ins2^Akita/Ins2⁺
• Genetic Background: involves: A/J * C57BL/6J * C57BL/6NSlc

homeostasis/metabolism

abnormal circulating glucose level ( J:112869 )

• increased fasting plasma glucose concentration in males

• increased plasma glucose at 30, 60, and 120 minutes of the intraperitoneal glucose tolerance test in males

Genotype
MGI:5510483

cx17

• Allelic Composition: Ins2^Akita/Ins2⁺; Rnf213^tm1.1Akoi/Rnf213^tm1.1Akoi
• Genetic Background: involves: C57BL/6N * C57BL/6NSlc

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:200802 )

N • mice exhibit normal insulin sensitivity and insulin plasma levels

decreased insulin secretion ( J:200802 )

• decreased total pancreatic insulin and prolinsulin content that is not as severe as in Ins2^Akita heterozygotes

increased circulating glucose level ( J:200802 )

• not as severe as in Ins2^Akita heterozygotes from 6 to 20 weeks

decreased circulating leptin level ( J:200802 )

impaired glucose tolerance ( J:200802 )

• not as severe as in Ins2^Akita heterozygotes

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:200802 )

• beta cells exhibit mild endoplasmic reticulum enlargement and slight mitochondria swelling that not as severe as in Ins2^Akita heterozygotes

decreased pancreatic beta cell number ( J:200802 )

• not as severe as in Ins2^Akita heterozygotes

decreased insulin secretion ( J:200802 )

• decreased total pancreatic insulin and prolinsulin content that is not as severe as in Ins2^Akita heterozygotes

behavior/neurological

increased food intake ( J:200802 )

• ot as much as in Ins2^Akita heterozygotes

growth/size/body

decreased body weight ( J:200802 )

• at 6 and 9 weeks but not 10 weeks compared with Ins2^Akita heterozygotes

• compared with Rnf213^tm1.1Akoi homozygotes

Genotype
MGI:3817777

cx18

• Allelic Composition: Ins2^Akita/Ins2⁺; Prf1^tm1Sdz/Prf1^tm1Sdz; Rag1^tm1Mom/Rag1^tm1Mom
• Genetic Background: NOD.Cg-Rag1^tm1Mom Ins2^Akita Prf1^tm1Sdz

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:138005 )

• islets exhibit progressively altered morphology

• insulin level is lower compared to Ins2-wild-type mice at 50 days of age and continues to diminish with age

hematopoietic system

increased erythrocyte cell number ( J:138005 )

• erythrocyte/erythocyte lineages (Ter 119+) are increased as compared to NOD controls

increased granulocyte number ( J:138005 )

• percentage of granulocytes is elevated compared to NOD/Lt

absent mature B cells ( J:138005 )

• lacking in mutant animals

absent T cells ( J:138005 )

• mature T cells are absent in mutant animals

increased macrophage cell number ( J:138005 )

• percentage of granulocytes is elevated

increased monocyte cell number ( J:138005 )

• percentage of granulocytes is elevated

immune system

increased granulocyte number ( J:138005 )

• percentage of granulocytes is elevated compared to NOD/Lt

absent mature B cells ( J:138005 )

• lacking in mutant animals

absent T cells ( J:138005 )

• mature T cells are absent in mutant animals

increased macrophage cell number ( J:138005 )

• percentage of granulocytes is elevated

increased monocyte cell number ( J:138005 )

• percentage of granulocytes is elevated

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:138005 )

N • spontaneously hyperglycemic mice are restored to euglycemia after receiving islet transplants at a dose of 4000 islet equivalents (IEQ) and remain euglycemic for the length of observation; at levels of 2000 and 3000 IEQ, mice display a drop in blood sugar, but eventually return to hyperglycemic status

abnormal glucose homeostasis ( J:138005 )

• glucose regulation is impaired as early as 3 weeks of age in nearly all mice

hyperglycemia ( J:138005 )

• male mice show greater susceptibility to develop hyperglycemia than females