Phenotypes associated with this allele

• Allele Symbol: Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}
• Allele Name: targeted mutation 1, Frances M Ashcroft
• Allele ID: MGI:3832575
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Gt(ROSA)26Sor^tm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor^+ Tg(Ins2-cre)23Herr/0	involves: 129S4/SvJae * C57BL/6	MGI:3832577
cn2	Gt(ROSA)26Sor^tm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor^+ Tg(Pdx1-cre/Esr1*)#Dam/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:5581814
cn3	Gt(ROSA)26Sor^tm1(Gck)Ydor/Gt(ROSA)26Sor^tm1(Kcnj11*V59M)Fmas Tg(Pdx1-cre/Esr1*)#Dam/0	involves: 129S4/SvJae * C57BL/6 * CBA	MGI:5581815
cn4	Gt(ROSA)26Sor^tm1(Kcnj11*V59M)Fmas/Gt(ROSA)26Sor^+ Tg(Nes-cre)1Kln/0	involves: 129S4/SvJae * C57BL/6 * SJL	MGI:4819394

Genotype
MGI:3832577

cn1

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}/Gt(ROSA)26Sor⁺; Tg(Ins2-cre)23Herr/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

Reduction in islet insulin content in Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}/Gt(ROSA)26Sor⁺ Tg(Ins2-cre)23Herr/0 mice

endocrine/exocrine glands

abnormal pancreatic islet morphology ( J:144715 )

• the percentage of islet area occupied by beta cells is somewhat decreased

abnormal pancreatic alpha cell morphology ( J:144715 )

• alpha cells are not confined to the islet mantle

increased pancreatic alpha cell number ( J:144715 )

• relative increase in the number of alpha cells

abnormal pancreatic beta cell morphology ( J:144715 )

• some of the beta cells are irregularly shaped

decreased pancreatic beta cell number ( J:144715 )

• the percentage of beta cells is decreased

abnormal pancreatic beta cell physiology ( J:144715 )

• reduction in islet insulin content by 5 weeks of age but not at 5 days of age

• K(sub)ATP currents in beta cells are larger compared to control cells an inhibition of these currents by glucose is impaired

• glucose induced calcium responses of beta cells are impaired

decreased insulin secretion ( J:144715 )

• impairment in basal and both first and second-phase glucose induced insulin secretion

homeostasis/metabolism

decreased insulin secretion ( J:144715 )

• impairment in basal and both first and second-phase glucose induced insulin secretion

increased circulating glucose level ( J:144715 )

• elevated glucose levels develop by P3

• overt diabetes develops by 5 weeks of age

increased circulating glucagon level ( J:144715 )

• slightly elevated

decreased circulating insulin level ( J:144715 )

growth/size/body

decreased body weight ( J:144715 )

• seen in males by 4 to 6 weeks of age

renal/urinary system

polyuria ( J:144715 )

• produce copious amounts of urine after when a few weeks old

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
permanent neonatal diabetes mellitus		DOID:0060639	OMIM:606176	J:144715

Genotype
MGI:5581814

cn2

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}/Gt(ROSA)26Sor⁺; Tg(Pdx1-cre/Esr1*)#Dam/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

homeostasis/metabolism

hyperglycemia ( J:210493 )

• severe in tamoxifen-treated mice without beta-cell apoptosis

Genotype
MGI:5581815

cn3

• Allelic Composition: Gt(ROSA)26Sor^tm1(Gck)Ydor/Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}; Tg(Pdx1-cre/Esr1*)#Dam/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * CBA

endocrine/exocrine glands

abnormal pancreatic beta cell physiology ( J:210493 )

• beta cells from tamoxifen-treated mice exhibit signs of DNA damage and apoptosis compared to control mice but to a lesser extent than in mice lacking Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}

homeostasis/metabolism

hyperglycemia ( J:210493 )

• severe in tamoxifen-treated mice

Genotype
MGI:4819394

cn4

• Allelic Composition: Gt(ROSA)26Sor^{tm1(Kcnj11*V59M)Fmas}/Gt(ROSA)26Sor⁺; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S4/SvJae * C57BL/6 * SJL

mortality/aging

perinatal lethality, incomplete penetrance ( J:162008 )

• mice, especially females, are born at less than Mendelian frequency

growth/size/body

decreased body weight ( J:162008 )

• trend towards lower body weight

behavior/neurological

impaired balance ( J:162008 )

• impaired balance control at 12 weeks of age

• take three times longer than controls to turn around on a thin rod suspended above the ground, and many fell off while attempting to do so

impaired coordination ( J:162008 )

• fall off a rotating rod earlier than control mice at 12 weeks of age

decreased grip strength ( J:162008 )

• unable to hang as long from an inverted screen or a horizontal bar at 12 weeks of age

hyperactivity ( J:162008 )

• more spontaneous activities than controls at 12 weeks of age

• stay significantly longer than controls in free-running wheels at 12 weeks of age

• run longer distance over a 23-hour period on a free-running wheel

nervous system

abnormal nervous system electrophysiology ( J:162008 )

• more hyperpolarized resting membrane potential of cerebellar Purkinje cells in acute brain slices than in controls

• restored by tolbutamide, a specific inhibitor of KATP channels

abnormal action potential ( J:162008 )

• substantially lower action potential frequency of cerebellar Purkinje cells in acute brain slices in both cell-attached and whole-cell recordings

• restored by tolbutamide

abnormal channel response ( J:162008 )

• the ATP sensitivity of the native muscle ATP-sensitive potassium (KATP) channel is reduced compared with that of control mice in patch-clamp recordings of isolated muscle fibers

muscle

muscle weakness ( J:162008 )

• unable to lift weights as effectively or to hang as long from an inverted screen or a horizontal bar at 12 weeks of age

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
permanent neonatal diabetes mellitus		DOID:0060639	OMIM:606176	J:162008