All Phenotypes Irs2<tm1Mfw> MGI Mouse

Phenotypes associated with this allele

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6272615
hm2	Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3583763
cn3	Gsk3b^tm2Jrw/Gsk3b^tm2Jrw Irs2^tm1Mfw/Irs2^tm1Mfw Tg(Ins2-cre)23Herr/?	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J	MGI:3802546
cx4	Insr^tm1Dac/Insr⁺ Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6	MGI:3653871
cx5	Irs2^tm1Mfw/Irs2^tm1Mfw Tg(Pdx1)#Mmy/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:6383732
cx6	Irs2^tm1Mfw/Irs2^tm1Mfw Tg(Ins2-Irs2)13Mfw/0	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3511011
cx7	Irs2^tm1Mfw/Irs2^tm1Mfw Ptpn1^tm1Bbk/Ptpn1^tm1Bbk	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3583981
cx8	Foxo1^tm1Whb/Foxo1⁺ Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3653870
cx9	Cdkn1b^tm1Kin/Cdkn1b^tm1Kin Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3529769
cx10	Cdkn1b^tm1Kin/Cdkn1b⁺ Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3529771
cx11	Gsk3b^tm1Jrw/Gsk3b⁺ Irs2^tm1Mfw/Irs2^tm1Mfw	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3802544

Allelic Composition	Irs2^tm1Mfw/Irs2^tm1Mfw
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)

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

vision/eye

short photoreceptor inner segment ( J:98107 )

• outer segments are shorter at 2 weeks

short photoreceptor outer segment ( J:98107 )

• the outer segments are shorter at P7 and 2 weeks of age

retina photoreceptor degeneration ( J:98107 )

• mice lose about 10% of photoreceptors 1 week after birth and up to 50% by 2 weeks of age

abnormal retina progenitor cell morphology ( J:98107 )

• the number of BrdU+ retinal precursors is decreased by about 40% at E12, indicating decreased cell proliferation in the embryo

• however, BrdU incorporation in the retina is similar to wild-type at 1 or 2 weeks of age

retina outer nuclear layer degeneration ( J:98107 )

• the outer nuclear layer is reduced about 10% at P7

• by 2 weeks of age, the retina is 50% thinner as a result of outer nuclear layer cell loss

• thinning of the outer nuclear layer is uniform throughout the retina and changes little from 2 to 6 weeks of age

• the number of apoptotic cells is increased in the outer nuclear layer, particularly between 1 and 2 weeks of age, but also at later time points

decreased total retina thickness ( J:98107 )

• by 2 weeks of age, the retina is 50% thinner as a result of outer nuclear layer cell loss however, the thickness of the inner nuclear layer or GCL are not decreased at 2 weeks of age

• however, retina is normal at 3 days of age

nervous system

short photoreceptor inner segment ( J:98107 )

• outer segments are shorter at 2 weeks

short photoreceptor outer segment ( J:98107 )

• the outer segments are shorter at P7 and 2 weeks of age

retina photoreceptor degeneration ( J:98107 )

• mice lose about 10% of photoreceptors 1 week after birth and up to 50% by 2 weeks of age

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

cellular

decreased oocyte number ( J:64791 )

• at E18.5, mutant ovaries contain decreased numbers of primary oocytes relative to wild-type ovaries

mortality/aging

premature death ( J:46134 , J:94000 )

• male mutants die prematurely from dehydration and hyperosomolar coma (J:46134)

• female mutants exhibit a similar disease progression but rarely die (J:46134)

• death due to diabetes (J:94000)

homeostasis/metabolism

abnormal circulating hormone level ( J:64791 )

decreased circulating testosterone level ( J:64791 )

• female homozygotes display reduced plasma testosterone levels relative to wild-type females in both dioestrous and oestrous states

decreased circulating estradiol level ( J:64791 )

• female homozygotes display reduced plasma estradiol levels relative to wild-type females in both dioestrous and oestrous states

decreased circulating luteinizing hormone level ( J:64791 )

• surprisingly, female homozygotes display low plasma luteinizing hormone levels relative to wild-type females in both dioestrous and oestrous states

decreased circulating prolactin level ( J:64791 )

• female homozygotes display low plasma prolactin levels relative to wild-type females

abnormal circulating insulin level ( J:94000 )

• elevated serum insulin levels at 6 weeks (before diabetes developed) and decreased insulin levels at 8 weeks with the onset of diabetes

increased circulating insulin level ( J:46134 , J:135659 )

• at >6 weeks, homozygotes display a 3-fold increase in fasting insulin levels relative to wild-type mice (J:46134)

• despite fasting hyperinsulinemia, homozygotes respond with a nearly 2-fold increase in insulin levels 60 minutes after glucose loading (J:46134)

• both fasting and fed insulin levels were higher than in wild-type mice (J:135659)

increased circulating leptin level ( J:64791 )

• as early as 4 weeks (i.e. prior to the onset of abnormal glucose tolerance) female homozygotes show a 2.5-fold increase in circulating leptin levels

• at 8 weeks, circulating leptin levels are increased by >5-fold relative to wild-type levels

decreased circulating progesterone level ( J:64791 )

• female homozygotes display reduced plasma progesterone levels relative to wild-type females in both dioestrous and oestrous states

abnormal energy homeostasis ( J:64791 )

• females homozygotes show hypothalamic resistance to leptin, suggesting defects in homeostatic mechanisms involved in leptin sensing and/or signaling

abnormal glucose homeostasis ( J:64791 , J:74303 )

	• homozygous males are more severely affected than age-matched females with respect to abnormal glucose homeostasis (J:64791)
	• immediately after treadmill exercise, male homozygotes show an attenuated increase in insulin-stimulated, phosphotyrosine-associated PI 3-kinase activity relative to wild-type males (J:74303) • however, insulin-stimulated, phosphotyrosine-associated PI 3-kinase response after exercise is slightly higher than the insulin-stimulated response alone (J:74303)

abnormal circulating glucose level ( J:74303 )

• treadmill exercise reduces blood glucose by ~20% in fasted wild-type mice but has no effect on blood glucose in fasted homozygotes

• plasma insulin concentrations are similar between wild-type and mutant mice at rest and remain unchanged after exercise

hyperglycemia ( J:46134 , J:94000 , J:96047 , J:135659 )

• homozygotes show increased levels of randomly fed sugars at postnatal day 3, and fasting hyperglycemia between 3 and 6 weeks of age (J:46134)

• at 10 weeks, homozygotes exhibit overt diabetes with fasting glucose levels of 323 35 mg dl^-1; if left untreated, the fasting sugar levels rise progressively to >400 mg dl^-1 at 12-16 weeks of age (J:46134)

• seen at about 10 weeks of age (J:96047)

• developed a progressive increase with severe hyperglycemia (J:135659)

• fasting glucose levels were higher than in wild-type mice (J:135659)

• developed in males between 4 and 6 weeks of age, which progressed to overt diabetes during the next 5-6 weeks until they died (J:94000)

impaired glucose tolerance ( J:46134 , J:64791 )

• at 6-8 weeks, homozygotes display significant glucose intolerance (>95% penetrance) during an intraperitoneal glucose-tolerance test (J:46134)

• by 6 weeks, male homozygotes are severely glucose intolerant (J:64791)

• in contrast, age-matched female homozygotes show only slightly increased blood glucose levels and mildly impaired glucose tolerance, suggesting sexual dimorphism in the diabetic phenotype (J:64791)

decreased skeletal muscle glycogen level ( J:74303 )

• at rest, fasted homozygotes tend to have reduced muscle glycogen levels relative to wild-type mice

• after treadmill exercise, homozygotes display significantly lower muscle glycogen levels than wild-type mice

insulin resistance ( J:46134 , J:135659 )

• homozygotes exhibit profound insulin resistance in both skeletal muscle and liver (J:46134)

• insulin resistant compared to wild-type (J:135659)

abnormal lipid homeostasis ( J:96047 )

• dyslipidemia

muscle

decreased skeletal muscle glycogen level ( J:74303 )

• at rest, fasted homozygotes tend to have reduced muscle glycogen levels relative to wild-type mice

• after treadmill exercise, homozygotes display significantly lower muscle glycogen levels than wild-type mice

behavior/neurological

polydipsia ( J:46134 )

polyphagia ( J:64791 )

• female homozygotes consume 30% more chow relative to wild-type females

abnormal mating frequency ( J:64791 )

• only 18.2% of female homozygotes vs 100% of wild-type display copulation plugs, suggesting abnormal oestrous cycle and sexual behavior

renal/urinary system

polyuria ( J:46134 )

• homozygotes display polyuria without ketosis

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:96047 )

• individual beta cell size is decreased

decreased pancreatic beta cell mass ( J:46134 , J:135659 )

• at 4 weeks, homozygotes show a significant reduction in pancreatic beta-cell mass indicating failure of compensatory islet hyperplasia (J:46134)

• no significant difference in non-beta endocrine-cell mass is observed (J:46134)

• reduced beta cell mass compared to wild-type (J:135659)

• decreased beta cell proliferation and increased beta cell accounts for reduction in beta cell mass (J:135659)

decreased pancreatic beta cell number ( J:94000 )

• at 8 weeks, islet area reduced by threefold due to 50% fewer beta cells

small pancreatic islets ( J:96047 )

• islet mass and density are significantly decreased compared to wild-type mice

decreased gonadotroph cell number ( J:64791 )

• mutant pituitaries contain ~40% less gonadotrophs than wild-type pituitaries

small pituitary gland ( J:64791 )

• mutant pituitaries are ~30% smaller

small pituitary intermediate lobe ( J:74303 )

• the size of the intermediate lobe is reduced more than that of other lobes

absent corpus luteum ( J:64791 )

• mutant ovaries show an almost complete absence of corpora lutea

abnormal ovarian follicle morphology ( J:64791 )

• at 6 weeks, mutant ovaries contain very few surface follicles and show thickening of the cortex relative to wild-type

decreased primary ovarian follicle number ( J:64791 )

• reduced numbers of primary follicles in adult ovaries

impaired ovarian folliculogenesis ( J:64791 )

• adult mutant ovaries contain reduced numbers of primary follicles with few growing follicles reaching an antral phase of development

small ovary ( J:64791 )

• at 6 weeks, female homozygotes show normal development of the external genitalia and reproductive tract; however, mutant ovaries are small relative to wild-type

growth/size/body

decreased birth body size ( J:46134 )

• homozygous neonates are 10% smaller than heterozygous or wild-type littermates

decreased body weight ( J:46134 , J:74303 )

	• homozygotes exhibit a small reduction in body weight that persists during weaning and into adulthood (J:46134)
	• at 5 weeks, male homozygotes weigh ~18% less than wild-type males (J:74303)

weight loss ( J:135659 )

• mice gained weight until about 9 weeks, and began to decline

obese ( J:64791 )

• female homozygotes weigh 20% more than wild-type females and are obese despite elevated leptin levels

nervous system

decreased gonadotroph cell number ( J:64791 )

• mutant pituitaries contain ~40% less gonadotrophs than wild-type pituitaries

small pituitary gland ( J:64791 )

• mutant pituitaries are ~30% smaller

small pituitary intermediate lobe ( J:74303 )

• the size of the intermediate lobe is reduced more than that of other lobes

reproductive system

absent corpus luteum ( J:64791 )

• mutant ovaries show an almost complete absence of corpora lutea

abnormal ovarian follicle morphology ( J:64791 )

• at 6 weeks, mutant ovaries contain very few surface follicles and show thickening of the cortex relative to wild-type

decreased primary ovarian follicle number ( J:64791 )

• reduced numbers of primary follicles in adult ovaries

impaired ovarian folliculogenesis ( J:64791 )

• adult mutant ovaries contain reduced numbers of primary follicles with few growing follicles reaching an antral phase of development

small ovary ( J:64791 )

• at 6 weeks, female homozygotes show normal development of the external genitalia and reproductive tract; however, mutant ovaries are small relative to wild-type

abnormal oogenesis ( J:64791 )

decreased oocyte number ( J:64791 )

• at E18.5, mutant ovaries contain decreased numbers of primary oocytes relative to wild-type ovaries

anovulation ( J:64791 )

• female homozygotes show features of anovulation, such as thickening of the ovarian stroma and absence of corpora lutea

failure of superovulation ( J:64791 )

• female homozygotes are resistant to exogenous gonadotropin stimulation

• however, uterine tissues of mutant females respond normally to exogenous sex steroids

absent estrous cycle ( J:64791 )

• 61% of female homozygotes fail to cycle and remain in an inactive or dioestrous state

female infertility ( J:64791 )

• when bred with homozygous mutant males, 0% of homozygous virgin females become pregnant during an 8-week period

• at <10 weeks, female homozygotes are relatively euglycemic and mildly insulin resistant, suggesting that female infertility is not a direct result of impaired glucose metabolism

reduced female fertility ( J:64791 )

• when bred with wild-type males, only 9% of homozygous virgin females (4-6-week-old) become pregnant during an 8-week period

reduced male fertility ( J:64791 )

• male homozygotes exhibit reduced fertility; males are adequate breeders only if mated prior to the onset of severe diabetes

adipose tissue

increased total body fat amount ( J:64791 )

• female homozygotes store twice as much body fat as age-matched wild-type females

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
type 2 diabetes mellitus		DOID:9352	OMIM:125853 OMIM:601283 OMIM:601407 OMIM:603694 OMIM:608036	J:46134

Allelic Composition	Gsk3b^tm2Jrw/Gsk3b^tm2Jrw Irs2^tm1Mfw/Irs2^tm1Mfw Tg(Ins2-cre)23Herr/?
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J * CBA/J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gsk3b^tm2Jrw mutation (2 available); any Gsk3b mutation (111 available)
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)
Tg(Ins2-cre)23Herr mutation (1 available)

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

homeostasis/metabolism

abnormal circulating glucose level ( J:135659 )

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

increased circulating insulin level ( J:135659 )

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

Allelic Composition	Insr^tm1Dac/Insr⁺ Irs2^tm1Mfw/Irs2^tm1Mfw
Genetic Background	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Insr^tm1Dac mutation (2 available); any Insr mutation (94 available)
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)

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

mortality/aging

postnatal lethality ( J:80826 )

homeostasis/metabolism

abnormal glucose homeostasis ( J:80826 )

• diabetic at 6 to 8 weeks of age

endocrine/exocrine glands

absent pancreatic beta cells ( J:80826 )

• undetectable at 8 weeks of age

Allelic Composition	Irs2^tm1Mfw/Irs2^tm1Mfw Tg(Pdx1)#Mmy/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)
Tg(Pdx1)#Mmy mutation (0 available)

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

vision/eye

abnormal retina layer morphology ( J:98107 )

• moderate cell loss is seen in the inner retinal layers at 16 months of age

retina photoreceptor degeneration ( J:98107 )

• mice exhibit progressive loss of photoreceptors at older ages, with most photoresceptors lost by 16 months of age

retina outer nuclear layer degeneration ( J:98107 )

• outer nuclear layer is reduced to one or two rows or is completely absent at 16 months of age

decreased total retina thickness ( J:98107 )

• mice exhibit similar reductions in retinal thickness at 1, 2, and 6 weeks of age as single Irs2^tm1Mfw homozygotes

nervous system

retina photoreceptor degeneration ( J:98107 )

• mice exhibit progressive loss of photoreceptors at older ages, with most photoresceptors lost by 16 months of age

Allelic Composition	Irs2^tm1Mfw/Irs2^tm1Mfw Tg(Ins2-Irs2)13Mfw/0
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)
Tg(Ins2-Irs2)13Mfw mutation (0 available)

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

mortality/aging

mortality/aging ( J:94000 )

N	• mice survived more than a year after single Irs2 homozygous mice died

vision/eye

abnormal b-wave implicit time ( J:98107 )

• rod-driven b-wave implicit time is delayed

decreased a-wave amplitude ( J:98107 )

• the amplitude of the a-wave is reduced at all flash intensities tested

decreased b-wave amplitude ( J:98107 )

• rod-driven b-wave amplitudes are reduced

abnormal cone electrophysiology ( J:98107 )

• light-adapted responses are reduced

• across stimulus conditions, cone ERGs are reduced on average to 64.9 % of control response, however the implicit time is not changed

abnormal rod electrophysiology ( J:98107 )

• dark-adapted ERGs are reduced

• across stimulus conditions, rod ERG responses are reduced on average to 34.9% of controls

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:94000 )

• increased proliferation and number of normal-sized beta cells compared to wild-type and single Irs2 homozygous mice

homeostasis/metabolism

increased circulating insulin level ( J:94000 )

• expression of Irs2 in beta cells resulted in a persistent compensatory hyperinsulinemia preventing the development of diabetes

• during intraperitoneal glucose challenge, no glucose intolerance was seen unlike in single Irs2 homozygous mice

Allelic Composition	Irs2^tm1Mfw/Irs2^tm1Mfw Ptpn1^tm1Bbk/Ptpn1^tm1Bbk
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)
Ptpn1^tm1Bbk mutation (2 available); any Ptpn1 mutation (36 available)

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

mortality/aging

premature death ( J:87249 )

• some double homozygous males survive for as long as 9 months; in contrast, Irs2^tm1Mfw homozygous males are severely diabetic and die around 15 weeks

growth/size/body

decreased body weight ( J:87249 )

• at 6 weeks, double homozygous males weigh 20% less than Irs2^tm1Mfw males

• by 15 weeks, Irs2^tm1Mfw males are severly diabetic and the difference in body weight becomes almost undetectable

homeostasis/metabolism

hyperglycemia ( J:87249 )

• at 15 weeks, double homozygotes exhibit fasting hyperglycemia

impaired glucose tolerance ( J:87249 )

• double homozygous males display improved glucose tolerance and delayed onset of diabetes relative to Irs2^tm1Mfw homozygous males

• however, double homozygotes still exhibit significant glucose intolerance at 6 and 15 weeks

increased insulin sensitivity ( J:87249 )

• at 6 weeks, young double homozygotes show increased peripheral insulin sensitivity; however, peripheral insulin sensitivity is reduced at 15 weeks

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:87249 )

• double homozygotes exhibit increased pancreatic cross-sectional beta-cell area relative to Irs2^tm1Mfw mice

pancreatic islet hyperplasia ( J:87249 )

• double homozygotes exhibit increased pancreatic islet size relative to Irs2^tm1Mfw mice

• despite compensatory islet growth and improved beta-cell function, double homozygotes develop diabetes at 15 weeks

Allelic Composition	Foxo1^tm1Whb/Foxo1⁺ Irs2^tm1Mfw/Irs2^tm1Mfw
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Foxo1^tm1Whb mutation (0 available); any Foxo1 mutation (31 available)
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)

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

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:80826 )

N	• near normal pancreatic beta cell area due to improved beta cell proliferation

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:80826 )

N	• no diabetes and normal life span

Allelic Composition	Cdkn1b^tm1Kin/Cdkn1b^tm1Kin Irs2^tm1Mfw/Irs2^tm1Mfw
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1b^tm1Kin mutation (1 available); any Cdkn1b mutation (25 available)
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)

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

endocrine/exocrine glands

increased pancreatic beta cell number ( J:96047 )

• beta cell proliferation and the total number of beta cells is increased compared to Irs2 single homozygotes; however the size of individual beta cells is similar to Irs2 single homozygotes

enlarged pancreatic islets ( J:96047 )

• islet mass, but not islet density, is significantly increased compared to Irs2 single homozygotes

homeostasis/metabolism

increased circulating glucose level ( J:96047 )

• double homozygotes have significantly elevated blood glucose levels at 18 weeks; however this elevation is slight compared to Irs2 single homozygotes

increased circulating insulin level ( J:96047 )

• fasting serum insulin levels are increased

Allelic Composition	Cdkn1b^tm1Kin/Cdkn1b⁺ Irs2^tm1Mfw/Irs2^tm1Mfw
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Find Mice

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

endocrine/exocrine glands

increased pancreatic beta cell number ( J:96047 )

• beta cell proliferation and the total number of beta cells are increased compared to Irs2 single homozygotes; however the size of individual beta cells is similar to Irs2 single homozygotes

enlarged pancreatic islets ( J:96047 )

• islet mass, but not islet density, is significantly increased compared to Irs2 single homozygotes

homeostasis/metabolism

increased circulating glucose level ( J:96047 )

• compound mutants have significantly elevated blood glucose levels at 18 weeks; however this elevation is slight compared to Irs2 single homozygotes

increased circulating insulin level ( J:96047 )

• fasting serum insulin levels are increased

Allelic Composition	Gsk3b^tm1Jrw/Gsk3b⁺ Irs2^tm1Mfw/Irs2^tm1Mfw
Genetic Background	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Gsk3b^tm1Jrw mutation (0 available); any Gsk3b mutation (111 available)
Irs2^tm1Mfw mutation (1 available); any Irs2 mutation (35 available)

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

cellular

abnormal pancreatic islet cell apoptosis ( J:135659 )

• beta cell apoptosis was reduced to compared to that in Irs2^tm1Mfw homozygous mice, however still higher than wild-type control

increased pancreatic beta cell proliferation ( J:135659 )

• increased beta cell proliferation accounts for preservation of beta cell mass

• normal beta cell mass unlike Irs2^tm1Mfw homozygous mice

growth/size/body

growth/size/body region phenotype ( J:135659 )

N	• retained normal weight through 12 weeks unlike Irs2^tm1Mfw homozygous mice

homeostasis/metabolism

abnormal circulating glucose level ( J:135659 )

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

increased circulating glucose level ( J:135659 )

• fasting glucose levels were higher than in wild-type mice at both 6 weeks and 8 weeks of age

• fasting glucose level were reduced relative to that in Irs2^tm1Mfw homozygous mice at 8 weeks but not at 6 weeks

increased circulating insulin level ( J:135659 )

• both fasting and fed insulin levels were higher than in wild-type mice

insulin resistance ( J:135659 )

• insulin resistant compared to wild-type

• no improvement over Irs2^tm1Mfw homozygous mice

endocrine/exocrine glands

abnormal pancreatic islet cell apoptosis ( J:135659 )

• beta cell apoptosis was reduced to compared to that in Irs2^tm1Mfw homozygous mice, however still higher than wild-type control

increased pancreatic beta cell proliferation ( J:135659 )

• increased beta cell proliferation accounts for preservation of beta cell mass

• normal beta cell mass unlike Irs2^tm1Mfw homozygous mice

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