Phenotypes associated with this allele

• Allele Symbol: Pten^tm1Mak
• Allele Name: targeted mutation 1, Tak W Mak
• Allele ID: MGI:1857937
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pten^tm1Mak/Pten^tm1Mak	involves: 129P2/OlaHsd * C57BL/6J	MGI:2179029
ht2	Pten^tm1Mak/Pten^+	B6.129P2-Pten^tm1Mak	MGI:3717269
ht3	Pten^tm1Mak/Pten^+	involves: 129P2/OlaHsd * C57BL/6J	MGI:2179030
cx4	Grhl3^tm1Jane/Grhl3^+ Pten^tm1Mak/Pten^+	involves: 129P2/OlaHsd * 129S1/Sv	MGI:5306661
cx5	Grb2^tm1Paw/Grb2^+ Pten^tm1Mak/Pten^+	involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3717274

Genotype
MGI:2179029

hm1

• Allelic Composition: Pten^tm1Mak/Pten^tm1Mak
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:50437 )

• die by E9.5

embryo

abnormal developmental patterning ( J:50437 )

• defective patterning of the cephalic and caudal regions

embryonic growth retardation ( J:50437 )

• embryos are developmentally delayed at E7.5

abnormal somite development ( J:50437 )

• fewer and less distinct somites

disorganized embryonic tissue ( J:50437 )

• E7.5 embryos are more compact and less organzied

abnormal allantois morphology ( J:50437 )

• display an expanded, loose and disorganized allantois

failure of chorioallantoic fusion ( J:50437 )

• fail to connect allantois and chorion

nervous system

abnormal brain development ( J:50437 )

• prominent and disproportionatea headfolds

growth/size/body

embryonic growth retardation ( J:50437 )

• embryos are developmentally delayed at E7.5

Genotype
MGI:3717269

ht2

• Allelic Composition: Pten^tm1Mak/Pten⁺
• Genetic Background: B6.129P2-Pten^tm1Mak

Embryonic defects in Pten^tm1Mak/Pten⁺

mortality/aging

embryonic lethality during organogenesis, incomplete penetrance ( J:93530 )

• more than 30% die by E10.5

growth/size/body

decreased embryo size ( J:93530 )

• the majority of embryos are smaller but have normal body symmetry and development of most organ systems

embryo

failure of initiation of embryo turning ( J:93530 )

• majority of embryos remain unturned

decreased embryo size ( J:93530 )

• the majority of embryos are smaller but have normal body symmetry and development of most organ systems

abnormal embryonic tissue morphology ( J:93530 )

• severely affected (about 5%) embryos have little or no development of the major organ systems, including the heart and brachial arches

• severely affected (about 5%) embryos have asymmetrical head folds

open neural tube ( J:93530 )

• neural tube is open along the entire length of the embryo

kinked neural tube ( J:93530 )

• neural tube is kinked along the entire length of the embyo

enlarged allantois ( J:93530 )

abnormal placenta morphology ( J:93530 )

• the remaining 20% of moribound embryos display other placental abnormalities including disorganization of the spongiotrophoblast layer and limited invasion of the trophoblast layer by the chorion

failure of chorioallantoic fusion ( J:93530 )

• the allantois fails to fuse to the chorion at E9 in 80% of dying embryos

nervous system

open neural tube ( J:93530 )

• neural tube is open along the entire length of the embryo

kinked neural tube ( J:93530 )

• neural tube is kinked along the entire length of the embyo

neoplasm

increased tumor incidence ( J:93530 )

increased adrenal gland tumor incidence ( J:93530 )

increased lymphoma incidence ( J:93530 )

increased endometrial carcinoma incidence ( J:93530 )

♀

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:93530 )

reproductive system

increased endometrial carcinoma incidence ( J:93530 )

♀

Genotype
MGI:2179030

ht3

• Allelic Composition: Pten^tm1Mak/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J

neoplasm

increased tumor incidence ( J:50437 )

• 14% develop spontaneous tumors during a 28 week observation period

increased adrenal gland tumor incidence ( J:63478 )

• 23% show marked expansion and proliferation of chromaffin cells of the adrenal medualla, consistent with medullary hyperplasia or pheochromocytoma; develop after 35 weeks of age

increased mammary gland tumor incidence ( J:63478 )

• 4% of mutants aged 26-29 weeks, 61% aged 30-49 weeks and 83% aged 50-65 weeks develop breast tumors, indicating an increased incidence of breast cancer as mice age

increased fibroadenoma incidence ( J:63478 )

• small breast tumors are classified as fibroadenoma

increased mammary adenocarcinoma incidence ( J:63478 )

• 49% of females develop breast tumors, most classified as Dunn's adenocarcinoma type C

increased prostate gland tumor incidence ( J:63478 )

♂

increased hamartoma incidence ( J:63478 )

• 9% show hamartomatous lesions involving the mucosa of the stomach, duodenum, small bowel, colon, or anorectal junction

increased leukemia incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

increased lymphoma incidence ( J:63478 )

• older mice develop a range of lymphomas

• 18% develop malignant lymphomas

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

increased carcinoma incidence ( J:50437 )

• 33% of tumors are teratocarcinoma

increased endometrial carcinoma incidence ( J:63478 )

♀ • 22% of females develop endometrial carcinoma, with the earliest case found at 30 weeks of age

increased incidence of tumors by ionizing radiation induction ( J:50437 )

• 19% of gamma-irradiated mutants develop tumors compared to none of wild-type

• tumors are thymic lymphomas/leukemias

digestive/alimentary system

enlarged Peyer's patches ( J:63478 )

• enlarged Peyer's patches composed of lymphohistiocytic infiltrates

colon polyps ( J:50437 )

• most mice exhibit microscopic hamartomatous polyps mainly in the colon

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:63478 )

• 23% show marked expansion and proliferation of chromaffin cells of the adrenal medualla, consistent with medullary hyperplasia or pheochromocytoma; develop after 35 weeks of age

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

increased mammary gland tumor incidence ( J:63478 )

• 4% of mutants aged 26-29 weeks, 61% aged 30-49 weeks and 83% aged 50-65 weeks develop breast tumors, indicating an increased incidence of breast cancer as mice age

increased fibroadenoma incidence ( J:63478 )

• small breast tumors are classified as fibroadenoma

increased mammary adenocarcinoma incidence ( J:63478 )

• 49% of females develop breast tumors, most classified as Dunn's adenocarcinoma type C

increased prostate gland tumor incidence ( J:63478 )

♂

abnormal seminiferous tubule morphology ( J:50437 )

♂ • most mice exhibit focal atrophic changes in the seminiferous tubules

reproductive system

increased prostate gland tumor incidence ( J:63478 )

♂

abnormal seminiferous tubule morphology ( J:50437 )

♂ • most mice exhibit focal atrophic changes in the seminiferous tubules

increased endometrial carcinoma incidence ( J:63478 )

♀ • 22% of females develop endometrial carcinoma, with the earliest case found at 30 weeks of age

endometrium hyperplasia ( J:63478 )

♀ • all females 26 weeks of age or older show endometrial hyperplasia

immune system

enlarged Peyer's patches ( J:63478 )

• enlarged Peyer's patches composed of lymphohistiocytic infiltrates

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

integument

increased mammary gland tumor incidence ( J:63478 )

• 4% of mutants aged 26-29 weeks, 61% aged 30-49 weeks and 83% aged 50-65 weeks develop breast tumors, indicating an increased incidence of breast cancer as mice age

increased fibroadenoma incidence ( J:63478 )

• small breast tumors are classified as fibroadenoma

increased mammary adenocarcinoma incidence ( J:63478 )

• 49% of females develop breast tumors, most classified as Dunn's adenocarcinoma type C

hematopoietic system

increased T cell derived lymphoma incidence ( J:50437 )

• 88% of the tumors are lymphoma/leukemia of the T-cell type

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Cowden syndrome		DOID:6457	OMIM:PS158350	J:63478
Cowden syndrome 1		DOID:0050657	OMIM:158350	J:63478

Genotype
MGI:5306661

cx4

• Allelic Composition: Grhl3^tm1Jane/Grhl3⁺; Pten^tm1Mak/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv

integument

increased skin papilloma incidence ( J:178952 )

• in DMBA/TPA treated mice

increased skin squamous cell carcinoma incidence ( J:178952 )

• in DMBA/TPA treated mice to a greater extent than in either single heterozygote

neoplasm

increased skin papilloma incidence ( J:178952 )

• in DMBA/TPA treated mice

increased skin squamous cell carcinoma incidence ( J:178952 )

• in DMBA/TPA treated mice to a greater extent than in either single heterozygote

Genotype
MGI:3717274

cx5

• Allelic Composition: Grb2^tm1Paw/Grb2⁺; Pten^tm1Mak/Pten⁺
• Genetic Background: involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * C57BL/6

endocrine/exocrine glands

increased adrenal gland tumor incidence ( J:93530 )

mortality/aging

mortality/aging ( J:93530 )

N • the embryonic lethality seen in Pten^tm1Mak heterozygotes is completely rescued

neoplasm

increased tumor incidence ( J:93530 )

• develop the same tumor types at the same frequency as Pten^tm1Mak heterozygotes, including neoplastic lesions in the breast, endometrium, prostate, adrenal gland, and lymphoid organs; tumor stage, grade, and metastatic potential are similar to that in Pten^tm1Mak heterozygotes

increased adrenal gland tumor incidence ( J:93530 )

increased lymphoma incidence ( J:93530 )

increased endometrial carcinoma incidence ( J:93530 )

♀

reproductive system

increased endometrial carcinoma incidence ( J:93530 )

♀