All Phenotypes Tg(Ins2-Akt1*)3Mbb MGI Mouse

Phenotypes associated with this allele

Allelic Composition	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Tg(Ins2-Akt1*)3Mbb/0
Genetic Background	B6.Cg-Rps6kb1^tm1Gtho Tg(Ins2-Akt1*)3Mbb

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rps6kb1^tm1Gtho mutation (1 available); any Rps6kb1 mutation (55 available)
Tg(Ins2-Akt1*)3Mbb mutation (0 available)

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

Beta cell and islet size in Tg(Ins2-Akt1*)3Mbb/0, Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho, and double mutant mice

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:144599 )

• increase in size of pancreatic beta cells

growth/size/body

decreased body weight ( J:144599 )

homeostasis/metabolism

decreased circulating glucose level ( J:144599 )

• decrease in fed and fasting glucose levels

• control of glycemia after injection of glucose is not affected

decreased circulating insulin level ( J:144599 )

• 35% reduction of plasma insulin levels

increased insulin sensitivity ( J:144599 )

• mice are more insulin sensitive than single Tg(Ins2-Akt1*)3Mbb

Allelic Composition	Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho Tg(Ins2-Akt1*)3Mbb/0
Genetic Background	B6.Cg-Rps6kb2^tm1Gtho Tg(Ins2-Akt1*)3Mbb

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rps6kb2^tm1Gtho mutation (0 available); any Rps6kb2 mutation (21 available)
Tg(Ins2-Akt1*)3Mbb mutation (0 available)

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

endocrine/exocrine glands

increased insulinoma incidence ( J:144599 )

• mice develop insulinomas with a 26% penetrance between 10 and 20 months of age

neoplasm

increased insulinoma incidence ( J:144599 )

• mice develop insulinomas with a 26% penetrance between 10 and 20 months of age

Allelic Composition	Rps6kb1^tm1Gtho/Rps6kb1^tm1Gtho Rps6kb2^tm1Gtho/Rps6kb2^tm1Gtho Tg(Ins2-Akt1*)3Mbb/0
Genetic Background	involves: 129P2/OlaHsd * C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Rps6kb1^tm1Gtho mutation (1 available); any Rps6kb1 mutation (55 available)
Rps6kb2^tm1Gtho mutation (0 available); any Rps6kb2 mutation (21 available)
Tg(Ins2-Akt1*)3Mbb mutation (0 available)

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

endocrine/exocrine glands

abnormal pancreatic beta cell morphology ( J:144599 )

• pancreatic beta cells are 4-fold larger than wild-type cells

neoplasm

neoplasm ( J:144599 )

N	• mice do not develop insulinomas

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

Tg(Ins2-Akt1*)3Mbb/0 mice develop insulinomas

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:144599 )

• 70% of mice show dysplastic islets with disorganized cells, irregular in shape and size

abnormal pancreatic beta cell morphology ( J:144599 )

• pancreatic beta cells are 5 times larger than wild-type cells

• beta cells have prominent nuclei with large nucleoli and are surrounded by dilated and asymmetric vessels

increased pancreatic beta cell mass ( J:144599 )

• increase in beta cell mass by 3.5-fold

enlarged pancreatic islets ( J:144599 )

• islet hypertrophy, as defined by large beta cells which maintain an organized structure with well-defined margins

pancreas fibrosis ( J:144599 )

• peripheral or infiltrating fibrosis is commonly seen in islets

increased pancreas tumor incidence ( J:144599 )

• mice develop pancreatic islet tumors in older age

increased insulinoma incidence ( J:144599 )

• 30% penetrance of insulinomas after 10 months of age

• insulinomas are classified as adenomas with rounded and encapsulated edges or multinodular adenomas with partial loss of the fibrous capsule

increased pancreatic islet cell carcinoma incidence ( J:144599 )

• 4 of 19 tumor cases are invasive carcinomas

• one case of lung metastasis is seen

• in the pancreatic carcinoma and lung metastasis, Brd-U positive malignant tumor cells are negative for the transgene and insulin expression and negative for neuroendocrine markers

homeostasis/metabolism

hypoglycemia ( J:144599 )

• hypoglycemia in the fed and fasted state

increased circulating insulin level ( J:144599 )

• 2.6-fold higher insulin levels at 3 months of age

improved glucose tolerance ( J:144599 )

• control of glycemia after injection of glucose is improved

mortality/aging

premature death ( J:144599 )

• lethality is increased after 1 year of age; death is preceded by hypoglycemia

neoplasm

increased pancreas tumor incidence ( J:144599 )

• mice develop pancreatic islet tumors in older age

increased insulinoma incidence ( J:144599 )

• 30% penetrance of insulinomas after 10 months of age

• insulinomas are classified as adenomas with rounded and encapsulated edges or multinodular adenomas with partial loss of the fibrous capsule

increased pancreatic islet cell carcinoma incidence ( J:144599 )

• 4 of 19 tumor cases are invasive carcinomas

• one case of lung metastasis is seen

• in the pancreatic carcinoma and lung metastasis, Brd-U positive malignant tumor cells are negative for the transgene and insulin expression and negative for neuroendocrine markers

Allelic Composition	Tg(Ins2-Akt1*)3Mbb/0
Genetic Background	involves: C57BL/6 * SJL

Find Mice

Using the International Mouse Strain Resource (IMSR)
No mouse lines available in IMSR.
See publication links below for author information.

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

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:72216 )

• 8-fold increase in islet mass

• islets have a reduced quantity of insulin when expressed per islet, but a slightly increased amount when normalized to cell number

• however, no changes in size of the pancreas

abnormal pancreatic beta cell morphology ( J:72216 )

• increase in the size of individual beta cells

• however, both alpha and delta cells appear normal

increased pancreatic beta cell mass ( J:72216 )

decreased pancreatic beta cell number ( J:72216 )

• decrease in the number of beta cells per islet

increased pancreatic islet number ( J:72216 )

enlarged pancreatic islets ( J:72216 )

abnormal pancreatic beta cell physiology ( J:72216 )

• 4.5-fold increase in pancreatic insulin

• however, glucagon levels are unchanged

• basal apoptosis is elevated about 2-fold in in beta cells

abnormal insulin secretion ( J:72216 )

• pancreas shows increased insulin secretion in response to elevations in glucose applied over time, however, when data are corrected for the increase in beta-cell mass, there is impaired secretion in response to glucose

homeostasis/metabolism

abnormal insulin secretion ( J:72216 )

decreased circulating glucose level ( J:72216 )

• mice exhibit mild fasting and fed hypoglycemia

increased circulating insulin level ( J:72216 )

improved glucose tolerance ( J:72216 )

• mice show a blunted excursion of blood glucose following a glucose load

• however, mice show a normal hypoglycemic response upon insulin administration and normal insulin responsiveness in the insulin tolerance test

decreased susceptibility to non-insulin-dependent diabetes ( J:72216 )

• mice are resistant to developing streptozotocin-induced diabetes mellitus

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