Phenotypes associated with this allele

• Allele Symbol: Stk11^tm1Keis
• Allele Name: targeted mutation 1, Kei Sakamoto
• Allele ID: MGI:3579498
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Stk11^tm1Keis/Stk11^tm1Keis	Not Specified	MGI:3580296
cn2	Stk11^tm1Keis/Stk11^tm1Keis Lyz2^tm1(cre)Ifo/Lyz2^+	involves: 129P2/OlaHsd	MGI:5470074
cn3	Pten^tm2Mak/Pten^tm2Mak Stk11^tm1Keis/Stk11^tm1Keis Tg(Cyp1a1-cre/ERT)1Dwi/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA	MGI:5789953
cn4	Stk11^tm1Keis/Stk11^tm1Keis Tg(Cyp1a1-cre/ERT)1Dwi/0	involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA	MGI:5789955
cn5	Stk11^tm1Keis/Stk11^tm1Keis Tg(Ckmm-cre)5Khn/0	involves: FVB	MGI:3580297
cn6	Stk11^tm1Keis/Stk11^tm1Keis Tg(Pomc1-cre)1Gsb/0	involves: FVB/N	MGI:4946518

Genotype
MGI:3580296

hm1

• Allelic Composition: Stk11^tm1Keis/Stk11^tm1Keis
• Genetic Background: Not Specified

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

mortality/aging

perinatal lethality, incomplete penetrance ( J:98513 )

• homozygous mice were born at approximately 30% lower than expected Mendelian frequency

reproductive system

male infertility ( J:98513 )

♂ • homozygous male mice are infertile, females are fertile

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:98513 )

N • displayed no overt phenotype up to the age of 10 weeks

N • possessed normal fasted and fed blood glucose levels

growth/size/body

growth/size/body region phenotype ( J:98513 )

N • normal growth from 4 to 10 weeks of age

Genotype
MGI:5470074

cn2

• Allelic Composition: Stk11^tm1Keis/Stk11^tm1Keis; Lyz2^tm1(cre)Ifo/Lyz2⁺
• Genetic Background: involves: 129P2/OlaHsd

immune system

increased circulating interleukin-10 level ( J:191723 )

• bone marrow derived macrophage show increased levels of LPS induced IL-10 mRNA and no further effect from addition PGE2 stimulation

homeostasis/metabolism

increased circulating interleukin-10 level ( J:191723 )

• bone marrow derived macrophage show increased levels of LPS induced IL-10 mRNA and no further effect from addition PGE2 stimulation

Genotype
MGI:5789953

cn3

• Allelic Composition: Pten^tm2Mak/Pten^tm2Mak; Stk11^tm1Keis/Stk11^tm1Keis; Tg(Cyp1a1-cre/ERT)1Dwi/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA

Urothelial hyperplasia and increased apoptosis in bladder epithelium of Pten^tm2Mak/Pten^tm2Mak Stk11^tm1Keis/Stk11^tm1Keis Tg(Cyp1a1-cre/ERT)1Dwi/0 mice

mortality/aging

premature death ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit decreased survival after day 100 of induction, mostly due to bladder blockage

neoplasm

increased urinary bladder carcinoma incidence ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen develop large papillary bladder tumors by day 125 of induction

• tumor tissue shows signs of spindle-shaped cells, squamous metaplasia, focal microvesicular change, and increase in nuclear-cytoplasmic ratio

renal/urinary system

enlarged urinary bladder ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit enlarged bladders by 125 days of induction

• treatment with rapamycin reduces bladder size

increased urinary bladder carcinoma incidence ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen develop large papillary bladder tumors by day 125 of induction

• tumor tissue shows signs of spindle-shaped cells, squamous metaplasia, focal microvesicular change, and increase in nuclear-cytoplasmic ratio

abnormal urinary bladder mucosa morphology ( J:169565 )

• by day 100 of induction with beta-napthoflavone and tamoxifen, mucosa of bladders is thickened

abnormal urinary bladder urothelium morphology ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit urothelial hyperplasia by day 50 and 100 of induction

• bladder epithelium of beta-napthoflavone and tamoxifen treated mice shows presence of apoptosis and vacuoles at day 50 of induction

• elevation in proliferation in the urothelium of mice injected with beta-napthoflavone and tamoxifen

• marker analysis indicates that bladder urothelial cells of beta-napthoflavone and tamoxifen injected mice exhibit characteristics of epithelial-mesenchymal transition, with loss of epithelial markers and increases in mesenchymal markers

• treatment with rapamycin reduces urothelial epithelium thickness and suppresses the epithelial-to-mesenchymal transition

urinary bladder obstruction ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen show bladder obstruction due to tumors

growth/size/body

enlarged urinary bladder ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen exhibit enlarged bladders by 125 days of induction

• treatment with rapamycin reduces bladder size

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
urinary bladder cancer		DOID:11054	OMIM:109800	J:169565

Genotype
MGI:5789955

cn4

• Allelic Composition: Stk11^tm1Keis/Stk11^tm1Keis; Tg(Cyp1a1-cre/ERT)1Dwi/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * C57BL/6J * CBA

digestive/alimentary system

gastric polyps ( J:169565 )

• mice injected with beta-napthoflavone and tamoxifen develop gastric polyps 270 days after induction

renal/urinary system

renal/urinary system phenotype ( J:169565 )

N • mice injected with beta-napthoflavone and tamoxifen do not show any abnormal bladder morphology and do not develop bladder tumors

Genotype
MGI:3580297

cn5

• Allelic Composition: Stk11^tm1Keis/Stk11^tm1Keis; Tg(Ckmm-cre)5Khn/0
• Genetic Background: involves: FVB

muscle

decreased muscle cell glucose uptake ( J:98513 )

• block of glucose uptake stimulated by 5-aminoimidazole-4-caroboxamide (AICAR) or by muscle contraction, but not by insulin

• possessed normal fasted and fed blood glucose levels

reproductive system

male infertility ( J:98513 )

♂ • homozygous male mice are infertile, female are fertile

growth/size/body

growth/size/body region phenotype ( J:98513 )

N • normal growth from 4 to 10 weeks of age

cellular

decreased muscle cell glucose uptake ( J:98513 )

• block of glucose uptake stimulated by 5-aminoimidazole-4-caroboxamide (AICAR) or by muscle contraction, but not by insulin

• possessed normal fasted and fed blood glucose levels

Genotype
MGI:4946518

cn6

• Allelic Composition: Stk11^tm1Keis/Stk11^tm1Keis; Tg(Pomc1-cre)1Gsb/0
• Genetic Background: involves: FVB/N

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:170130 )

N • mice exhibit normal energy expenditure, leptin concentration, and fasted plasma insulin levels

N • male mice exhibit normal glucose metabolism

abnormal gluconeogenesis ( J:170130 )

• hepatic glucose production induced by pyruvate or insulin is increased compared to in wild-type mice

impaired glucose tolerance ( J:170130 )

• in female mice, but not male mice

abnormal glycogen homeostasis ( J:170130 )

• female mice exhibit reduced whole-body glycogen synthesis compared with wild-type mice

insulin resistance ( J:170130 )

• after an insulin tolerance test, female mice exhibit reduced glucose clearance compared with wild-type mice

behavior/neurological

decreased fluid intake ( J:170130 )

• in mice treated with MT2

• however, unstimulated food intake is normal

endocrine/exocrine glands

endocrine/exocrine gland phenotype ( J:170130 )

N • male and female mice exhibit normal pancreatic islet architecture, beta cell mass, and function

nervous system

nervous system phenotype ( J:170130 )

N • mice exhibit normal POMC neuron numbers compared with wild-type mice

N • POMC neurons exhibit normal glucose sensing