Phenotypes associated with this allele

• Allele Symbol: Stk11^tm1Tpm
• Allele Name: targeted mutation 1, Tomi P Makela
• Allele ID: MGI:2387003
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Stk11^tm1Tpm/Stk11^tm1Tpm	Not Specified	MGI:3790876
ht2	Stk11^tm1Tpm/Stk11^+	involves: 129S7/SvEvBrd * C57BL/6 * CD-1	MGI:3790955
ht3	Stk11^tm1Tpm/Stk11^+	Not Specified	MGI:3790954
cx4	Ptgs2^tm1Jed/Ptgs2^tm1Jed Stk11^tm1Tpm/Stk11^+	involves: 129S7/SvEvBrd * C57BL/6 * CD-1	MGI:3790956
cx5	Ptgs2^tm1Jed/Ptgs2^+ Stk11^tm1Tpm/Stk11^+	involves: 129S7/SvEvBrd * C57BL/6 * CD-1	MGI:3790958

Genotype
MGI:3790876

hm1

• Allelic Composition: Stk11^tm1Tpm/Stk11^tm1Tpm
• Genetic Background: Not Specified

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:70892 )

• no viable embryos are observed past E11.0

embryo

abnormal placental labyrinth vasculature morphology ( J:70892 )

• invasion of placenta by embryonic blood vessels does not occur; at E9.5 lack of fetal blood vessels in rudimentary labyrinth layer is shown by absence of VEGF signal

abnormal vitelline vasculature morphology ( J:70892 )

• rudimentary vessels are seen between the parietal and visceral leaves of yolk sac; vessels are congested with nucleated embryonic blood cells

• vitelline artery is completely atretic

absent vitelline blood vessels ( J:70892 )

• large vessels and extensive capillary network fail to develop in mutant yolk sac

placenta hemorrhage ( J:70892 )

• at E9.5, placentas are hemorrhagic and edematous

• blood lacunae have ruptured causing massive hemorrhaging by E10.5

absent first pharyngeal arch ( J:70892 )

• absent in some embryos after E8.25

first pharyngeal arch hypoplasia ( J:70892 )

• hypoplastic in some embryos after E8.25

abnormal embryo turning ( J:70892 )

• after E8.25, failure of embryo turning is observed

abnormal head mesenchyme morphology ( J:70892 )

• cephalic mesenchyme of E9.5 head folds has lower cell density and fewer capillaries than controls; cell density is result of increased cell death assayed by TUNEL staining and this apoptosis phenotype is limited to the E9.5 embryos

abnormal neural fold formation ( J:70892 )

• at E9.5 folds often display large cystic degenerations near dorsal aorta with some containing embryonic blood cells

abnormal neural tube closure ( J:70892 )

• defect in neural tube closure is observed after E8.25

abnormal notochord morphology ( J:70892 )

• misaligned and contorted along anterior/posterior axis of embryo at E9.25

abnormal somite development ( J:70892 )

• somitogenesis is defective resulting in dimorphic protrusive somites at E9.5

abnormal spongiotrophoblast layer morphology ( J:70892 )

• less organized than in wild-type and contains larger number of abnormal (flt-1 negative) giant cells

small placenta ( J:70892 )

• diameter of placenta is smaller at E9.5

abnormal visceral yolk sac morphology ( J:70892 )

delayed chorioallantoic fusion ( J:70892 )

• fusion is delayed in mutant conceptuses compared to controls, but occurs by E9.5

cardiovascular system

abnormal dorsal aorta morphology ( J:70892 )

• at E8.5, vessel is thin and discontinuous especially in the anterior part

• at E9.5 lumen remains thin with intersomitic branches ending prematurely in the mesenchyme

abnormal placental labyrinth vasculature morphology ( J:70892 )

• invasion of placenta by embryonic blood vessels does not occur; at E9.5 lack of fetal blood vessels in rudimentary labyrinth layer is shown by absence of VEGF signal

abnormal vitelline vasculature morphology ( J:70892 )

• rudimentary vessels are seen between the parietal and visceral leaves of yolk sac; vessels are congested with nucleated embryonic blood cells

• vitelline artery is completely atretic

absent vitelline blood vessels ( J:70892 )

• large vessels and extensive capillary network fail to develop in mutant yolk sac

abnormal vascular smooth muscle morphology ( J:70892 )

• complete absence of vascular smooth muscle cell (VSMC) staining is observed in mutant dorsal aorta and somites at E9.5

• strong ectopic VSMC signal is observed in head folds

placenta hemorrhage ( J:70892 )

• at E9.5, placentas are hemorrhagic and edematous

• blood lacunae have ruptured causing massive hemorrhaging by E10.5

craniofacial

absent first pharyngeal arch ( J:70892 )

• absent in some embryos after E8.25

first pharyngeal arch hypoplasia ( J:70892 )

• hypoplastic in some embryos after E8.25

muscle

abnormal vascular smooth muscle morphology ( J:70892 )

• complete absence of vascular smooth muscle cell (VSMC) staining is observed in mutant dorsal aorta and somites at E9.5

• strong ectopic VSMC signal is observed in head folds

nervous system

abnormal neural tube closure ( J:70892 )

• defect in neural tube closure is observed after E8.25

growth/size/body

abnormal head mesenchyme morphology ( J:70892 )

• cephalic mesenchyme of E9.5 head folds has lower cell density and fewer capillaries than controls; cell density is result of increased cell death assayed by TUNEL staining and this apoptosis phenotype is limited to the E9.5 embryos

Genotype
MGI:3790955

ht2

• Allelic Composition: Stk11^tm1Tpm/Stk11⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CD-1

digestive/alimentary system

intestine polyps ( J:93361 )

• polyposis detected at 4-5 months

• treatment with celecoxib (Ptgs2 inhibitor) between 3.5 and 10 months reduces number of large polyps observed; similar results are obtained when treatment is performed at 6.5-10 months in mice on 129S7/SvEvBrd * CD-1 background

• microvessel density is reduced in polyps with celecoxib treatment

gastric polyps ( J:93361 )

• polyposis detected at 4-5 months

• treatment with celecoxib (Ptgs2 inhibitor) between 3.5 and 10 months reduces number of large polyps observed; similar results are obtained when treatment is performed at 6.5-10 months in mice on 129S7/SvEvBrd * CD-1 background

• microvessel density is reduced in polyps with celecoxib treatment

neoplasm

decreased tumor incidence ( J:93361 )

• 86% decrease in tumor burden is seen at 10 months in mice treated with celecoxib between 3.5 and 10 months compared to untreated controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Peutz-Jeghers syndrome		DOID:3852	OMIM:175200	J:93361

Genotype
MGI:3790954

ht3

• Allelic Composition: Stk11^tm1Tpm/Stk11⁺
• Genetic Background: Not Specified

mortality/aging

premature death ( J:79074 )

• 80% die by 16 months of age

growth/size/body

distended abdomen ( J:79074 )

• noted as mice age

digestive/alimentary system

intestine polyps ( J:79074 )

duodenum polyps ( J:79074 )

• grossly distended by large polyps

gastric polyps ( J:79074 )

• all mice >6 months of age have macroscopic gastrointestinal polyps; majority are found in glandular stomach with equal distribution in fundus, antrum, and pylorus

• in most animals, 1-3 large polyps (20-30 mm in diameter) originate in pylorus and protrude into duodenum

• all polyps have extensive well-developed smooth muscle component originating from central stalk contiguous with muscularis mucosa

intestinal obstruction ( J:79074 )

• results from protrusion of large polyps into lumen

neoplasm

increased hepatocellular carcinoma incidence ( J:79074 )

• seen in one animal; incidence similar to age-matched controls

increased liver adenoma incidence ( J:79074 )

• small number of tumors and neoplasias are observed in various organs including multiple liver adenomas in mice 6-20 months of age; incidence similar to age-matched controls

increased hemangioma incidence ( J:79074 )

• seen in one animal; incidence similar to age-matched controls

increased endometrial carcinoma incidence ( J:79074 )

♀ • seen in one animal; incidence similar to age-matched controls

liver/biliary system

increased hepatocellular carcinoma incidence ( J:79074 )

• seen in one animal; incidence similar to age-matched controls

increased liver adenoma incidence ( J:79074 )

• small number of tumors and neoplasias are observed in various organs including multiple liver adenomas in mice 6-20 months of age; incidence similar to age-matched controls

reproductive system

increased endometrial carcinoma incidence ( J:79074 )

♀ • seen in one animal; incidence similar to age-matched controls

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Peutz-Jeghers syndrome		DOID:3852	OMIM:175200	J:79074

Genotype
MGI:3790956

cx4

• Allelic Composition: Ptgs2^tm1Jed/Ptgs2^tm1Jed; Stk11^tm1Tpm/Stk11⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CD-1

digestive/alimentary system

intestine polyps ( J:93361 )

• large polyps (>2 mm) are reduced in number compared to Stk11 heterozygotes at 8.5 months

gastric polyps ( J:93361 )

• large polyps (>2 mm) are reduced in number compared to Stk11 heterozygotes at 8.5 months

neoplasm

decreased tumor incidence ( J:93361 )

• 53-54% decrease in tumor burden is seen at 10 months in mice treated with celecoxib between 3.5 and 10 months compared to untreated controls

Genotype
MGI:3790958

cx5

• Allelic Composition: Ptgs2^tm1Jed/Ptgs2⁺; Stk11^tm1Tpm/Stk11⁺
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * CD-1

digestive/alimentary system

intestine polyps ( J:93361 )

• large polyps (>2 mm) are reduced in number compared to Stk11 heterozygotes at 8.5 months

gastric polyps ( J:93361 )

• large polyps (>2 mm) are reduced in number compared to Stk11 heterozygotes at 8.5 months