Phenotypes associated with this allele

• Allele Symbol: Stk11^tm1.1Rdp
• Allele Name: targeted mutation 1.1, Ronald DePinho
• Allele ID: MGI:2387402
• Summary: 17 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Stk11^tm1.1Rdp/Stk11^+	involves: 129S6/SvEvTac * C57BL/6 * SJL	MGI:3814532
cn2	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp	involves: 129S6/SvEvTac	MGI:5527248
cn3	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5659883
cn4	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp	involves: 129S6/SvEvTac * FVB/N	MGI:3774861
cn5	Stk11^tm1.1Rdp/Stk11^tm1.2Rdp	involves: 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5659884
cn6	Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh Nras^tm1.1Nesh/Nras^tm1.1Nesh Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tg(Tyr-cre/ERT2)13Bos/0	B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1.1Nesh Cdkn2a^tm2.1Nesh Stk11^tm1.1Rdp	MGI:5752239
cn7	Kras^tm4Tyj/Kras^+ Stk11^tm1.1Rdp/Stk11^tm1.2Rdp	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5659881
cn8	Kras^tm4Tyj/Kras^+ Stk11^tm1.1Rdp/Stk11^tm1.1Rdp	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * FVB/N	MGI:5659880
cn9	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tg(PLAT-cre)116Sdu/0	involves: 129S6/SvEvTac	MGI:7341367
cn10	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Isl1^tm1(cre)Tmj/Isl1^+	involves: 129S6/SvEvTac * 129X1/SvJ	MGI:5524150
cn11	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tg(Nes-cre)1Kln/0	involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL	MGI:5524151
cn12	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tg(Pdx1-cre)89.1Dam/0	involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N * ICR	MGI:3814590
cn13	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tg(KRT14-cre)1Ipc/0	involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL	MGI:3814722
cn14	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp H2az2^Tg(Wnt1-cre)11Rth/H2az2^+	involves: 129S6/SvEvTac * C57BL/6J * CBA/J	MGI:6711690
cn15	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tg(Sprr2f-cre)1Dcas/0	involves: 129S6/SvEvTac * FVB/N	MGI:4438263
cn16	Stk11^tm1.1Rdp/Stk11^tm1.1Rdp Tagln^tm1(cre/ERT2)Feil/Tagln^+	involves: 129S/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:3814824
cn17	Stk11^tm1.1Rdp/Stk11^+ Tagln^tm1(cre/ERT2)Feil/Tagln^+	involves: 129S/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL	MGI:3814821

Genotype
MGI:3814532

ht1

• Allelic Composition: Stk11^tm1.1Rdp/Stk11⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * SJL

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

normal phenotype

no abnormal phenotype detected ( J:78818 )

• animals are born at expected frequency and show no gross abnormalities

Genotype
MGI:5527248

cn2

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp
• Genetic Background: involves: 129S6/SvEvTac

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:174020 )

N • mice treated with a cre-expressing adenovirus in the liver exhibit normal serum insulin and liver triglyceride levels under fed and fasted conditions

abnormal circulating glucose level ( J:174020 )

• mice treated with a cre-expressing adenovirus in the liver exhibit partial abrogation of glucose lowering effects of adiponectin compared with wild-type mice

increased circulating glucose level ( J:174020 )

• in mice treated with a cre-expressing adenovirus in the liver under both fasted and fed conditions

abnormal gluconeogenesis ( J:174020 )

• mice treated with a cre-expressing adenovirus in the liver exhibit partially blocked adiponectin effect on hepatic glucose production compared with wild-type mice

Genotype
MGI:5659883

cn3

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

neoplasm

neoplasm ( J:124682 )

N • mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation do not develop pulmonary neoplasia

Genotype
MGI:3774861

cn4

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

neoplasm

increased endometrial carcinoma incidence ( J:131865 )

♀ • 65% of female mice develop endometrial carcinomas within nine months of having a Cre-expressing adenovirus injected into the lumen of their uterus

♀ • tumors maintained polarity of cells found in normal endometrial glands

♀ • the majority of tumors were confined to the uterus with one being diffusely metastatic throughout the peritoneum

♀ • in some tumors, the mitotic activity and apoptotic index were significantly altered compared to normal endometrium tissue from the same mouse

reproductive system

increased endometrial carcinoma incidence ( J:131865 )

♀ • 65% of female mice develop endometrial carcinomas within nine months of having a Cre-expressing adenovirus injected into the lumen of their uterus

♀ • tumors maintained polarity of cells found in normal endometrial glands

♀ • the majority of tumors were confined to the uterus with one being diffusely metastatic throughout the peritoneum

♀ • in some tumors, the mitotic activity and apoptotic index were significantly altered compared to normal endometrium tissue from the same mouse

Genotype
MGI:5659884

cn5

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.2Rdp
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N

neoplasm

neoplasm ( J:124682 )

N • mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation do not develop pulmonary neoplasia

Genotype
MGI:5752239

cn6

• Allelic Composition: Cdkn2a^tm2.1Nesh/Cdkn2a^tm2.1Nesh; Nras^tm1.1Nesh/Nras^tm1.1Nesh; Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tg(Tyr-cre/ERT2)13Bos/0
• Genetic Background: B6J.Cg-Tg(Tyr-cre/ERT2)13Bos Nras^tm1.1Nesh Cdkn2a^tm2.1Nesh Stk11^tm1.1Rdp

integument

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-hydroxytamoxifen (4-OHT) neonatally or in adulthood exhibit enhanced nevus formation

• mice treated with 4-OHT neonatally develop melanoma with 85% penetrance and a median latency of 22.1 weeks

neoplasm

increased cutaneous melanoma incidence ( J:220627 )

• mice treated with 4-hydroxytamoxifen (4-OHT) neonatally or in adulthood exhibit enhanced nevus formation

• mice treated with 4-OHT neonatally develop melanoma with 85% penetrance and a median latency of 22.1 weeks

increased metastatic potential ( J:220627 )

• 36% of mice treated with 4-OHT neonatally that develop melanoma show macrometastatic spread to lymph nodes, lung, spleen and/or liver

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
skin melanoma		DOID:8923	OMIM:608035 OMIM:612263	J:220627

Genotype
MGI:5659881

cn7

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Stk11^tm1.1Rdp/Stk11^tm1.2Rdp
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * FVB/N

mortality/aging

premature death ( J:124682 )

• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a mean survival of 9 weeks after ad-cre inoculation

neoplasm

increased metastatic potential ( J:124682 )

• regional lymph-node metastases and axial skeleton metastases are seen in 61% of ad-cre inoculated mice

increased lung tumor incidence ( J:124682 )

• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants

increased lung adenocarcinoma incidence ( J:124682 )

• adenocarcinoma is seen in all metastatic lesions

increased lung large cell carcinoma incidence ( J:124682 )

• 2 of 27 ad-cre treated mice show large cell carcinoma

increased lung squamous cell carcinoma incidence ( J:124682 )

• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas

• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC

respiratory system

increased lung tumor incidence ( J:124682 )

• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants

increased lung adenocarcinoma incidence ( J:124682 )

• adenocarcinoma is seen in all metastatic lesions

increased lung large cell carcinoma incidence ( J:124682 )

• 2 of 27 ad-cre treated mice show large cell carcinoma

increased lung squamous cell carcinoma incidence ( J:124682 )

• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas

• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung non-small cell carcinoma		DOID:3908		J:124682

Genotype
MGI:5659880

cn8

• Allelic Composition: Kras^tm4Tyj/Kras⁺; Stk11^tm1.1Rdp/Stk11^tm1.1Rdp
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6 * FVB/N

mortality/aging

premature death ( J:124682 )

• mice inoculated with an adenovirus expressing cre recombinase (ad-cre) by inhalation have a median survival of 9 weeks after ad-cre inoculation

neoplasm

increased metastatic potential ( J:124682 )

• regional lymph-node metastases and axial skeleton metastases are seen in 61% of ad-cre inoculated mice

increased lung tumor incidence ( J:124682 )

• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants

increased lung adenocarcinoma incidence ( J:124682 )

• adenocarcinoma is seen in all metastatic lesions

increased lung large cell carcinoma incidence ( J:124682 )

• 2 of 27 ad-cre treated mice show large cell carcinoma

increased lung squamous cell carcinoma incidence ( J:124682 )

• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas

• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC

respiratory system

increased lung tumor incidence ( J:124682 )

• mice inoculated with ad-cre develop lung tumors; tumor burden is increased at early time points and larger lesions at later time points are seen than in single Kras mutants

increased lung adenocarcinoma incidence ( J:124682 )

• adenocarcinoma is seen in all metastatic lesions

increased lung large cell carcinoma incidence ( J:124682 )

• 2 of 27 ad-cre treated mice show large cell carcinoma

increased lung squamous cell carcinoma incidence ( J:124682 )

• 56% of ad-cre treated mice develop squamous cell carcinomas (SCCs) or adenosquamous carcinomas

• squamous tumors do not express pro-surfactant protein, but express pan-keratin and p63, markers of SCC

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
lung non-small cell carcinoma		DOID:3908		J:124682

Genotype
MGI:7341367

cn9

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tg(PLAT-cre)116Sdu/0
• Genetic Background: involves: 129S6/SvEvTac

mortality/aging

neonatal lethality, complete penetrance ( J:236402 )

• all newborns are unable to feed normally and die during the first day after birth

craniofacial

abnormal craniofacial morphology ( J:236402 )

• newborns show severe craniofacial abnormalities

abnormal basicranium morphology ( J:236402 )

• at P0, cephalic neural crest cells (CNCC)-derived bones of the cranial base show significant surface reduction

• in contrast, mesodermal-derived occipital bones (e.g. basioccipital bone) are unaffected

small cranium ( J:236402 )

abnormal neurocranium morphology ( J:236402 )

• at P0, some bones of the skull vault, esp. the frontal bone, show significant surface reduction

large anterior fontanelle ( J:236402 )

• anterior fontanel is wide open at P0

small frontal bone ( J:236402 )

small parietal bone ( J:236402 )

abnormal sphenoid bone morphology ( J:236402 )

• sphenoid alae show significant surface reduction

small basisphenoid bone ( J:236402 )

small presphenoid bone ( J:236402 )

small temporal bone squamous part ( J:236402 )

• squamous temporal bone shows significant surface reduction

abnormal alveolar process morphology ( J:236402 )

• although mandibles are shorter, they exhibit a distinct hyperplasia at the alveolar part of the mandible

short mandible ( J:236402 )

• average mandible length is significantly reduced

small premaxilla ( J:236402 )

small maxilla ( J:236402 )

micrognathia ( J:236402 )

abnormal nasal bone morphology ( J:236402 )

• nasal bone exhibits increased porosity

• however, nasal bone surface area is unaffected

abnormal palatine bone morphology ( J:236402 )

• palatine shows significant surface reduction

small vomer bone ( J:236402 )

cleft secondary palate ( J:236402 )

• newborns exhibit a large cleft of the secondary palate

short snout ( J:236402 )

• newborns exhibit a shortened nose

skeleton

abnormal basicranium morphology ( J:236402 )

• at P0, cephalic neural crest cells (CNCC)-derived bones of the cranial base show significant surface reduction

• in contrast, mesodermal-derived occipital bones (e.g. basioccipital bone) are unaffected

small cranium ( J:236402 )

abnormal neurocranium morphology ( J:236402 )

• at P0, some bones of the skull vault, esp. the frontal bone, show significant surface reduction

large anterior fontanelle ( J:236402 )

• anterior fontanel is wide open at P0

small frontal bone ( J:236402 )

small parietal bone ( J:236402 )

abnormal sphenoid bone morphology ( J:236402 )

• sphenoid alae show significant surface reduction

small basisphenoid bone ( J:236402 )

small presphenoid bone ( J:236402 )

small temporal bone squamous part ( J:236402 )

• squamous temporal bone shows significant surface reduction

abnormal alveolar process morphology ( J:236402 )

• although mandibles are shorter, they exhibit a distinct hyperplasia at the alveolar part of the mandible

short mandible ( J:236402 )

• average mandible length is significantly reduced

small premaxilla ( J:236402 )

small maxilla ( J:236402 )

micrognathia ( J:236402 )

abnormal nasal bone morphology ( J:236402 )

• nasal bone exhibits increased porosity

• however, nasal bone surface area is unaffected

abnormal palatine bone morphology ( J:236402 )

• palatine shows significant surface reduction

small vomer bone ( J:236402 )

decreased bone mineral density ( J:236402 )

• many bones of the skull exhibit osteopenia

decreased bone ossification ( J:236402 )

• at P0, head skeleton shows both ossification and cartilage defects

growth/size/body

abnormal alveolar process morphology ( J:236402 )

• although mandibles are shorter, they exhibit a distinct hyperplasia at the alveolar part of the mandible

abnormal nasal bone morphology ( J:236402 )

• nasal bone exhibits increased porosity

• however, nasal bone surface area is unaffected

cleft secondary palate ( J:236402 )

• newborns exhibit a large cleft of the secondary palate

short snout ( J:236402 )

• newborns exhibit a shortened nose

decreased body height ( J:236402 )

• newborns exhibit a reduced stature

digestive/alimentary system

cleft secondary palate ( J:236402 )

• newborns exhibit a large cleft of the secondary palate

behavior/neurological

abnormal suckling behavior ( J:236402 )

• newborns are unable to feed normally

respiratory system

abnormal nasal bone morphology ( J:236402 )

• nasal bone exhibits increased porosity

• however, nasal bone surface area is unaffected

Genotype
MGI:5524150

cn10

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Isl1^tm1(cre)Tmj/Isl1⁺
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ

mortality/aging

decreased tumor-free survival time ( J:201695 )

• mice are euthanized at 4 to 6 weeks due to massive gastrointestinal tumors

• however, mice survive to birth and postnatally

neoplasm

increased gastrointestinal tumor incidence ( J:201695 )

• massive gastrointestinal tumors

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:201695 )

• massive gastrointestinal tumors

nervous system

nervous system phenotype ( J:201695 )

N • axon bundles are normal in the brainstem trigeminal complex, ascending tracts in the spinal cord (spinocerebellar, spinothalamic and dorsal funiculus), the optic nerve and motor and sensory nerves in the periphery

N • mice exhibit normal type Ia proprioceptive sensory neuron projections to the ventral horn

N • mice exhibit no sensory or motor deficit

abnormal cerebral cortex morphology ( J:201695 )

• axons tracts in the cortical intermediate zone are reduced compared to in control mice

thin cerebral cortex ( J:201695 )

• thin-walled

behavior/neurological

behavior/neurological phenotype ( J:201695 )

N • mice exhibit no sensory or motor deficit

Genotype
MGI:5524151

cn11

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tg(Nes-cre)1Kln/0
• Genetic Background: involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6 * SJL

nervous system

nervous system phenotype ( J:201695 )

N • mice exhibit normal type Ia proprioceptive sensory neuron projections to the ventral horn

Genotype
MGI:3814590

cn12

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tg(Pdx1-cre)89.1Dam/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * CBA * FVB/N * ICR

digestive/alimentary system

abnormal exocrine pancreas morphology ( J:134078 )

• metaplastic lesions are observed with contributions from acinar and ductal cells consistent with active acinar-ductal transdifferentiation

abnormal pancreatic acinus morphology ( J:134078 )

• at P1 acinar units are less compact with distended lumens; in some regions, acinar units are fragmented and intermixed with endocrine cells

abnormal pancreatic acinar cell morphology ( J:134078 )

• from P2 to P8, a rapid loss of acinar cells is observed, associated with appearance of abnormal ductal structures

endocrine/exocrine glands

increased pancreas apoptosis ( J:134078 )

• at P3, TUNEL assays reveal an 18-fold increase in acinar cell death in the pancreas relative to controls

abnormal exocrine pancreas morphology ( J:134078 )

• metaplastic lesions are observed with contributions from acinar and ductal cells consistent with active acinar-ductal transdifferentiation

abnormal pancreatic acinus morphology ( J:134078 )

• at P1 acinar units are less compact with distended lumens; in some regions, acinar units are fragmented and intermixed with endocrine cells

abnormal pancreatic acinar cell morphology ( J:134078 )

• from P2 to P8, a rapid loss of acinar cells is observed, associated with appearance of abnormal ductal structures

abnormal pancreatic islet morphology ( J:134078 )

• islets are smaller and less well aggregated at P1 with a more diffuse distribution relative to wild-type; aggregation of islets is delayed with accumulation of smaller islets by P16

• at P1, there are decreased numbers of alpha, beta, and delta cells in the pancreas

decreased pancreatic alpha cell number ( J:134078 )

• at P1

decreased pancreatic beta cell number ( J:134078 )

• at P1

decreased pancreatic delta cell number ( J:134078 )

• at P1

small pancreatic islets ( J:134078 )

• islets are smaller and less well aggregated at P1 with a more diffuse distribution relative to wild-type; aggregation of islets is delayed with accumulation of smaller islets by P16

small pancreas ( J:134078 )

• at P1, pancreas is smaller than in littermate controls

pancreas fibrosis ( J:134078 )

• from P2 to P8, reactive fibrosis is observed in conjunction with acinar cell loss and abnormal ductal structures

pancreas inflammation ( J:134078 )

homeostasis/metabolism

increased circulating glucose level ( J:134078 )

• at P1, mice have elevated blood glucose levels but these return to normal by P8

improved glucose tolerance ( J:134078 )

• adult mutants show improved beta cell function relative to wild-type with faster clearance of blood glucose

cellular

increased pancreas apoptosis ( J:134078 )

• at P3, TUNEL assays reveal an 18-fold increase in acinar cell death in the pancreas relative to controls

immune system

pancreas inflammation ( J:134078 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Peutz-Jeghers syndrome		DOID:3852	OMIM:175200	J:134078

Genotype
MGI:3814722

cn13

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tg(KRT14-cre)1Ipc/0
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * FVB/N * SJL

growth/size/body

decreased body size ( J:131037 )

• animals are smaller than controls

neoplasm

increased squamous cell carcinoma incidence ( J:131037 )

• some mice develop SCC (spontaneously) by 40 weeks of age (>20%)

• all DMBA-treated mutant mice develop invasive skin cancers determined to be SCC with an average latency of 8 weeks, whereas no DMBA-treated controls develop cancer

vision/eye

cornea opacity ( J:131037 )

• due to hyperkeratinization of corneal epithelium

integument

delayed hair appearance ( J:131037 )

• mice show delayed hair growth

sparse hair ( J:131037 )

• adult hair is less dense than in controls

waved hair ( J:131037 )

• adult hair is wavy

abnormal hair shaft morphology ( J:131037 )

• hair shaft diameter is reduced relative to controls

abnormal hair follicle morphology ( J:131037 )

• mild follicular plugging (keratinous debris filling follicular openings) is observed

reddish skin ( J:131037 )

• increased relative to controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Peutz-Jeghers syndrome		DOID:3852	OMIM:175200	J:131037

Genotype
MGI:6711690

cn14

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; H2az2^{Tg(Wnt1-cre)11Rth}/H2az2⁺
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6J * CBA/J

nervous system

abnormal axon extension ( J:305107 )

• dorsal root ganglia explants from E13.5 embryos exhibit reduced axonal growth in vitro compared with control samples

• however, sensory neurons exhibit normal polarization

abnormal axon morphology ( J:305107 )

• E13.5 limbs exhibit strongly reduced overall axonal coverage and total number of axonal branches compared with control limbs

• however, no increase in apoptosis is observed and mitochondria motility is normal

abnormal neuron physiology ( J:305107 )

• reduced axonal ATP levels

cellular

abnormal axon extension ( J:305107 )

• dorsal root ganglia explants from E13.5 embryos exhibit reduced axonal growth in vitro compared with control samples

• however, sensory neurons exhibit normal polarization

Genotype
MGI:4438263

cn15

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tg(Sprr2f-cre)1Dcas/0
• Genetic Background: involves: 129S6/SvEvTac * FVB/N

mortality/aging

premature death ( J:158190 )

• females display a marked increase in mortality; females begin to die at 17 weeks of age and all females are dead by 30 weeks

• death in most animals is infiltration of endometrial cancer into the urinary bladder

• 4 weeks of daily rapamycin treatment (started around 30 weeks) extended lifespan to 36 weeks+ compared to untreated control mutants

neoplasm

increased metastatic potential ( J:158190 )

• endometrial carcinoma spreads to adjacent organs in older animals

• distant metastases (such as pulmonary or subcutaneous nodules) are observed infrequently

increased endometrial carcinoma incidence ( J:158190 )

♀ • female mortality results from invasive endometrial cancers

♀ • tumor infiltration is progressive throughout the uteri resulting in diffuse uterine enlargement with increasing age

♀ • uteri develop normally and are normal in size through onset of sexual maturity, but by 16 weeks of age there is significant uterine enlargement; in females surviving to 28 weeks, the average uterine weight is increased around 10 fold relative to controls

♀ • by 12 weeks of age, diffuse infiltration of the myometrium is observed in most animals

♀ • in older animals endometrial carcinoma spreads to adjacent organs, most significantly the ovary, cervix and bladder

♀ • daily intraperitoneal rapamycin injections for 4 weeks (started around 30 weeks) slowed significantly slowed progression, resulting in 2.4 fold decrease in mean uterine weights; tumor burden is reduced and increased apoptotic cell death is detected in endometrial epithelial cells

reproductive system

increased endometrial carcinoma incidence ( J:158190 )

♀ • female mortality results from invasive endometrial cancers

♀ • tumor infiltration is progressive throughout the uteri resulting in diffuse uterine enlargement with increasing age

♀ • uteri develop normally and are normal in size through onset of sexual maturity, but by 16 weeks of age there is significant uterine enlargement; in females surviving to 28 weeks, the average uterine weight is increased around 10 fold relative to controls

♀ • by 12 weeks of age, diffuse infiltration of the myometrium is observed in most animals

♀ • in older animals endometrial carcinoma spreads to adjacent organs, most significantly the ovary, cervix and bladder

♀ • daily intraperitoneal rapamycin injections for 4 weeks (started around 30 weeks) slowed significantly slowed progression, resulting in 2.4 fold decrease in mean uterine weights; tumor burden is reduced and increased apoptotic cell death is detected in endometrial epithelial cells

abnormal myometrium morphology ( J:158190 )

♀ • by 12 weeks of age, diffuse infiltration of the myometrium is observed in most animals

abnormal uterus size ( J:158190 )

♀ • uteri develop normally and are normal in size through onset of sexual maturity, but by 16 weeks of age there is significant uterine enlargement; in females surviving to 28 weeks, the average uterine weight is increased around 10 fold relative to controls

♀ • tumor infiltration is progressive throughout the uteri resulting in diffuse uterine enlargement with increasing age

increased uterus weight ( J:158190 )

♀ • by 16 weeks of age, there is significant uterine enlargement and in

renal/urinary system

hydronephrosis ( J:158190 )

• results from infiltration of endometrial carcinoma into the bladder

abnormal urinary bladder morphology ( J:158190 )

• uteri develop normally and are normal in size through onset of sexual maturity, but by 16 weeks of age there is significant uterine enlargement; in females surviving to 28 weeks, the average uterine weight is increased around 10 fold relative to controls

• tumor infiltration is progressive throughout the uteri resulting in diffuse uterine enlargement with increasing age

urinary bladder obstruction ( J:158190 )

• urinary tract obstruction result from tumor infiltration into the bladder

digestive/alimentary system

peritoneal inflammation ( J:158190 )

• invasion through uterine wall results in peritonitis in some animals, contributing to morbity

immune system

peritoneal inflammation ( J:158190 )

• invasion through uterine wall results in peritonitis in some animals, contributing to morbity

sepsis ( J:158190 )

• invasion through uterine wall results in sepsis in some animals, contributing to morbity

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
endometrial cancer		DOID:1380	OMIM:608089	J:158190

Genotype
MGI:3814824

cn16

• Allelic Composition: Stk11^tm1.1Rdp/Stk11^tm1.1Rdp; Tagln^{tm1(cre/ERT2)Feil}/Tagln⁺
• Genetic Background: involves: 129S/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

digestive/alimentary system

gastrointestinal tract polyps ( J:134476 )

• 75% of tamoxifen-treated animals develop gastrointestinal polyposis by 11 months

• average size of polyps is comparable to that seen in double heterozygotes

increased gastrointestinal tumor incidence ( J:134476 )

• tumor formation (polyposis) in the gastrointestinal tract is increased greatly relative to controls

neoplasm

increased gastrointestinal tumor incidence ( J:134476 )

• tumor formation (polyposis) in the gastrointestinal tract is increased greatly relative to controls

Genotype
MGI:3814821

cn17

• Allelic Composition: Stk11^tm1.1Rdp/Stk11⁺; Tagln^{tm1(cre/ERT2)Feil}/Tagln⁺
• Genetic Background: involves: 129S/Sv * 129X1/SvJ * C57BL/6 * CD-1 * SJL

mortality/aging

premature death ( J:134476 )

• almost 50% of tamoxifen-treated animals die by 18 months from gastrointestinal obstruction (average lifespan 13.5 months); widespread gastrointestinal polyposis is found at time of necropsy

digestive/alimentary system

digestive/alimentary phenotype ( J:134476 )

N • with 2 intraperitoneal injections of tamoxifen at 6 weeks of age, no abnormalities are seen at 3 and 8 months of age

gastrointestinal tract polyps ( J:134476 )

• at 11 months, gastrointestinal tract polyps are observed in <60% of tamoxifen-treated animals

• average polyp size is smaller than in Stk11^tm1.2Rdp/+ mice at 11 months

increased gastrointestinal tumor incidence ( J:134476 )

• tumor formation (polyposis) in the gastrointestinal tract is increased greatly relative to controls

• tumors are characterized by a smooth muscle core, abundant stroma and hyperplastic epithelia without dysplasia

intestinal obstruction ( J:134476 )

• at 11 months, mice present with severe gastrointestinal obstruction

neoplasm

increased gastrointestinal tumor incidence ( J:134476 )

• tumor formation (polyposis) in the gastrointestinal tract is increased greatly relative to controls

• tumors are characterized by a smooth muscle core, abundant stroma and hyperplastic epithelia without dysplasia