Mouse Genome Informatics
ht1
    Ptentm1Hwu/Pten+
involves: 129S4/SvJae * BALB/c
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• Background Sensitivity: spectrum of tumor incidence and onset on the BALB/c background are similar to Ptentm1.1Hwu on the BALB/c background in the first seven months


Mouse Genome Informatics
cn2
    Ptentm1Hwu/Ptentm1Hwu
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• prostate adenocarcinoma is seen by 9-10 weeks of age in mutants infected with an adenovirus expressing Cre recombinase (J:144810)
• mutants infected with an adenovirus expressing Cre recombinase develop PIN by 7 weeks of age (J:144810)

muscle
• primary myotube cultures treated with adenovirus-cre to delete Pten results in increased myotube size
• primary myotube cultures treated with adenovirus-cre do not exhibit the palmitate-induced decrease in cell size seen in control myotubes

homeostasis/metabolism
• mice injected neonatally with a cre-expressing adenovirus into the sensorimotor cortex and undergoing pyramidotomy in adulthood exhibit an increase in trans-midline sprouting of adult corticospinal tract axons compared to controls
• neonatal and postnatal deletion of Pten by injecting cre-expressing adenovirus into the sensorimotor cortex at the neonatal stage or 4 weeks of age, respectively, results in increased corticospinal tract regeneration following T8 complete spinal cord crush injury compared to controls
• the increase in corticospinal tract regeneration is seen when complete spinal cord crush is done at 2 and 5 months of age and the regenerating axons follow ectopic trajectories and extend bilaterally in contrast with normal unilateral extension in controls
• regenerating corticospinal tract axons after injury from mice injected with cre-expressing adenovirus are able to reform synaptic structures in the spinal cord caudal to the lesion site


Mouse Genome Informatics
cn3
    Kdrtm1Jrt/Kdr+
Ptentm1Hwu/Ptentm1Hwu
Twist2tm1.1(cre)Dor/Twist2+

B6.129-Twist2tm1.1(cre)Dor Kdrtm1Jrt Ptentm1Hwu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
cardiovascular system
• vasculogenesis defect
• impaired differentiation of angioblasts into mature endothelial cells and blood vessels

respiratory system
• increase in angioblasts in E18.5 lungs


Mouse Genome Informatics
cn4
    Ptentm1Hwu/Ptentm1Hwu
Twist2tm1.1(cre)Dor/Twist2+

B6.129-Twist2tm1.1(cre)Dor Ptentm1Hwu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants with less severe phenotypes die within 2-3 hours of birth, displaying cyanosis, chest retractions, and dyspnea
• lethality between E15.5 and E18.5

respiratory system
• increase in collagen deposition in the lungs
• alveolar spaces are frequently lined by cuboidal cells with immature lamellar bodies
• reduction in distal capillary network density in E15.5 lungs
• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5
• increase in the distance between the capillaries and the lumen of the airways
• marker analysis indicates expansion of the distal epithelial progenitor cell domain
• E18.5 lungs exhibit a hypercellular mesenchymal compartment
• more than 5-fold increase in the number of CD45-CD31+ embryonic mesenchymal progenitor side population (E-SP) and CD45-CD31- E-SP cell populations in E17.5 lungs indicating an increase in lung mesenchymal progenitor cell populations
• in mutants with less severe phenotypes that die within hours of birth

cardiovascular system
• reduction in distal capillary network density in E15.5 lungs
• the capillary network is misaligned with corresponding respiratory airways (airway/capillary uncoupling or dysplasia) at E18.5
• increase in the distance between the capillaries and the lumen of the airways
• 44% of embryos lack of vascularization in entire embryos at E15.5
• E15.5 embryos show lack of vascularization in organs such as limbs and liver
• impaired differentiation of angioblasts into mature endothelial cells and blood vessels
• 15% of embryos exhibit hemorrhage at E18.5

homeostasis/metabolism
• newborns show a decrease in blood oxygenation
• in mutants with less severe phenotypes that die within hours of birth


Mouse Genome Informatics
cn5
    Ptentm1Hwu/Ptentm1Hwu
Tg(Gdf9-cre)5092Coo/0

B6.Cg-Ptentm1Hwu Tg(Gdf9-cre)5092Coo
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age (J:131827)
• at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells (J:131827)
• follicular structure at 12 weeks of age is deformed and luteolysis is observed (J:131827)
• reduction in follicle death and clearance before and around the time of sexual maturity (J:131827)
• at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles (J:131827)
• growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further (J:131827)
• premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood (J:131827)
• percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%) (J:131827)
• by p23, no primordial follicles an be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage (J:131827)
• at P8, ovaries appear larger with more activated follicles (J:131827)
• by P23 and 35, ovaries remain larger and contain more activated follicles (J:131827)

homeostasis/metabolism
• increase in levels of follicle-stimulating hormone at 12-20-week old females
• increase in levels of luteinizing hormone at 12-20-week old females

reproductive system
• luteolysis is observed (degeneration of corpora lutea) at 12 weeks of age (J:131827)
• at P8, ovaries appear larger with more activated follicles, including transient follicles containing enlarged oocytes surrounded by flattened pregranulosa cells, primary follicles with enlarged oocytes surrounded by one layer of cuboidal granulosa cells and some secondary follicles with two layers of granulosa cells (J:131827)
• follicular structure at 12 weeks of age is deformed and luteolysis is observed (J:131827)
• reduction in follicle death and clearance before and around the time of sexual maturity (J:131827)
• at 7 weeks of age, ovaries show increased numbers of transient and preantral type 5 follicles (J:131827)
• growth dynamics of activated transient follicles is different than in controls, with some follicles remaining at the transient stage whereas others develop further (J:131827)
• premature activation of the primordial follicle pool resulting in depletion of primordial follicles in early adulthood (J:131827)
• percentage of primordial follicles in ovaries at P8 is lower (49.6%) than in controls (83.6%) (J:131827)
• by p23, no primordial follicles an be identified in mutants compared to 69.2% of follicles in controls areas are still at the primordial stage (J:131827)
• at P8, ovaries appear larger with more activated follicles (J:131827)
• by P23 and 35, ovaries remain larger and contain more activated follicles (J:131827)
• accelerated oocyte growth (J:131827)
• many transient follicles contain degraded oocytes (J:131827)
• females exhibit activation of the pool of primordial follicles that leads to follicle depletion, causing premature ovarian failure (J:131827)
• many transient follicles contain degraded oocytes suggesting that some prematurely activated follicles undergo atresia (J:131827)
• older females exhibit irregular estrous cycles (J:131827)
• females become infertile in early adulthood, after 12-13 weeks of age (J:131827)


Mouse Genome Informatics
cn6
    Ptentm1Hwu/Ptentm1Hwu
Tg(Nkx2-1-cre)2Sand/0

B6.Cg-Ptentm1Hwu Tg(Nkx2-1-cre)2Sand
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• at P14, thyroid architecture is altered, with multilayered epithelial cells surrounding the colloid lumen and with some dysmorphic follicles containing abnormal material inside
• dysmorphic follicles containing abnormal material inside and multiple degenerative follicles which have varying degrees of colloid depletion are seen at P14
• increase in thyroid size is already seen at E15.5 and is striking by P14
• increase in epithelial cell proliferation rate at E15.5 and P14
• Background Sensitivity: at P14, epithelial cell proliferation rates are higher on the congenic C57BL/6 background than on the BALB/c background

homeostasis/metabolism
• decrease in T4 hormonal levels at P14

mortality/aging
• all mutants die before 2 weeks of age due to compression of the trachea and esophagus by the enlarged thyroid

tumorigenesis
• at P14, thyroid structure is completely altered with multiple degenerative follicles, which have varying degrees of colloid depletion, resembling a follicular adenoma


Mouse Genome Informatics
cn7
    Ptentm1Hwu/Pten+
Tg(Nkx2-1-cre)2Sand/0

B6.Cg-Ptentm1Hwu Tg(Nkx2-1-cre)2Sand
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• altered thyroid structure with normal areas that include colloid-filled follicles and normal areas with focal hyperplasia, polynuclear cells, small nonencapsulated areas of hypercellularity with solid and/or mircofollicular patterns and internal hemorrhage

homeostasis/metabolism
• P14 mutants show a mild decrease of T4 but normal TSH

tumorigenesis
• 100% of mutants develop differentiated follicular tumors of the thyroid after about 2 years of age

Mouse Models of Human Disease
OMIM IDRef(s)
Thyroid Carcinoma, Follicular; FTC 188470 J:197590


Mouse Genome Informatics
cn8
    Ptentm1Hwu/Ptentm1Hwu
Tg(Tyr-cre)1Lru/0

B6.Cg-Ptentm1Hwu Tg(Tyr-cre)1Lru
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die between 13 and 20 days after birth

growth/size
• although mutants are similar in weight and size as wild-type mice on P2, they fail to gain as much weight over the next 20 days as controls

digestive/alimentary system
• mutants exhibit some intraluminal bubbles along the gastrointestinal tract
• mutants exhibit intestinal pseudoobstruction
• dilatation of the cecum
• mutants exhibit intestinal pseudoobstruction

nervous system
• hypertrophy and hyperplasia of the myenteric and submucosal plexus in the enteric nervous system by 2 weeks of age resulting in ganglioneuromatosis
• enteric ganglia are bigger than in wild-type at P15
• hyperplasia is observed in enteric neuronal cells at E17.5 while hypertrophy of enteric neuronal cells is only seen after birth and not during embryonic development

pigmentation
• hyperpigmentation in the tail, pinna, paws, skin, and olfactory bulb


Mouse Genome Informatics
cn9
    Ptentm1Hwu/Ptentm1Hwu
Tg(Zp3-cre)93Knw/0

B6.Cg-Ptentm1Hwu Tg(Zp3-cre)93Knw
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• mice exhibit normal follicular development, showing healthy corpora lutea and preovulatory follicles at 16 weeks of age, normal resumption of meiosis, ovulation, fertilization and fertility, although PI3K-Akt signaling is elevated (J:151696)


Mouse Genome Informatics
cn10
    Ptentm1Hwu/Ptentm1Hwu
Rfwd2tm2.1Vmd/Rfwd2tm2.1Vmd
Tg(Pbsn-cre)4Prb/0

B6N.Cg-Rfwd2tm2.1Vmd Ptentm1Hwu Tg(Pbsn-cre)4Prb
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• invasive in 11 of 13 mice at 30 weeks of age (J:172653)
• high grade in 2 of 13 mice at 30 weeks of age (J:172653)


Mouse Genome Informatics
cn11
    Ptentm1Hwu/Ptentm1Hwu
Tg(Mx1-cre)1Cgn/0

BKS.Cg-Ptprcb Thy1a Tg(Mx1-cre)1Cgn Ptentm1Hwu
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants become ill shortly after pIpC treatment and exhibit lethargy, ruffling of fur, and hunched posture and die from leukemia

hematopoietic system
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus
• increase in blast cell frequency after pIpC administration to induce Cre expression
• mice treated with polyinosine-polycytidine (pIpC) to induce Cre expression exhibit extramedullary hematopoiesis, with prominent expansion in the number of immature myeloid cells
• mice develop myeloproliferative disease shortly after pIpC administration to induce Cre expression with complete effacement of the splenic architecture
• reduction in bone marrow cellularity after pIpC administration to induce Cre expression
• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression
• mice treated with pIpC to induce Cre expression exhibit an increase in hematopoietic stem cell proliferation but become depleted, most likely due to inhibition of self-renewal as no increase in cell death was observed
• mutants maintained on rapamycin after pIpC treatment do not exhibit expansion of hematopoietic stem cells

immune system
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus
• 10-fold increase in spleen cellularity after pIpC administration to induce Cre expression

tumorigenesis
• within 4-6 weeks after pIpC treatment, most mutants progress to leukemia, including acute myeloid leukemia and acute lymphoblastic leukemia
• mutants maintained on rapamycin after pIpC treatment do not develop leukemia
• seen in mutants within 4-6 weeks after pIpC treatment
• seen in mutants within 4-6 weeks after pIpC treatment

endocrine/exocrine glands
• mice treated with pIpC to induce Cre expression exhibit an enlarged thymus


Mouse Genome Informatics
cn12
    Pik3catm1Jjz/Pik3catm1Jjz
Pik3cbtm1Jjz/Pik3cbtm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0

FVB.Cg-Pik3catm1Jjz Pik3cbtm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
N
• mutants do not develop hamartomas over a period of 300 days and epidermal thickness is normal at 8 weeks of age (J:199362)


Mouse Genome Informatics
cn13
    Pik3catm1Jjz/Pik3catm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0

FVB.Cg-Pik3catm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• expanded basal cell layers
• development of skin lesions is delayed and severity is reduced compared to single Pten mutants
• develop skin hamartomas with a median latency of 121 days
• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants

tumorigenesis
• develop skin hamartomas with a median latency of 121 days


Mouse Genome Informatics
cn14
    Pik3cbtm1Jjz/Pik3cbtm1Jjz
Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0

FVB.Cg-Pik3cbtm1Jjz Ptentm1Hwu Tg(KRT14-cre)#Smr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• accumulation of terminally differentiated suprabasal cells
• development of skin lesions is delayed and severity is reduced compared to single Pten mutants
• develop skin hamartomas with a median latency of 131 days
• skin is thickened at 8 weeks of age, but to a lesser extent than in single Pten mutants

tumorigenesis
• develop skin hamartomas with a median latency of 131 days


Mouse Genome Informatics
cn15
    Ptentm1Hwu/Ptentm1Hwu
Tg(KRT14-cre)#Smr/0

FVB.Cg-Ptentm1Hwu Tg(KRT14-cre)#Smr
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
integument
• marker analysis indicates a perturbed basal-to-suprabasal transition
• expanded suprabasal layer as indicated by an increase in Keratin 10-postive cells
• increase in the number of epidermal cell layers at 8 weeks of age
• progressive development of multiple dermal lesions after weaning
• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age
• median onset of disease is 62 days
• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required
• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions
• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis
• at 8 weeks of age

tumorigenesis
• multiple cutaneous hamartomas are seen all over the body within 12 weeks of age
• median onset of disease is 62 days
• mice treated with BKM120, a pan-class I PI3K inhibitor, beginning at 3 weeks of age, do not develop PTEN hamartoma tumor syndrome skin lesions; removal of BKM120 results in development of lesions, indicating that continuous treatment is required
• mice with advanced multiple skin hamartomas treated with BKM120 show improved skin conditions
• papillomatous lesions around the facial orifices, ears, and paws, with most associated with hyperkeratosis


Mouse Genome Informatics
cn16
    Calcatm1.1(cre/ERT2)Ptch/Calca+
Trp53tm1Brn/Trp53tm1Brn
Rb1tm2Brn/Rb1tm2Brn
Ptentm1Hwu/Ptentm1Hwu

involves: 129 * 129P2/OlaHsd * 129S4/SvJae * BALB/c * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• death within 3 months of tamoxifen treatment

respiratory system
• increased proliferation of pulmonary neuroendocrine cells

tumorigenesis
• increased invasiveness at 2.5 months after tamoxifen treatment
• small cell lung tumors 2.5 months after tamoxifen treatment
• all mice develop thyroid tumors


Mouse Genome Informatics
cn17
    Gt(ROSA)26Sortm1(cre/ERT)Nat/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu

involves: 129 * 129S4/SvJae * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most females that develop lymphomas die at about 9 weeks post-4OHT injection
• all mutants die from tumor burden by 45 weeks post-4OHT injection

tumorigenesis
• treatment of mice with 4OHT at 6 weeks of age to induce cre-mediated recombination results in tumor formation with a mean latency of 17 weeks
• multiple tumors are seen in 27.3% of 4OHT-treated mice
• 46.1% of females develop endometrial cancer after 4OHT treatment
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment
• 76.9% incidence of lymphomas in females after 4OHT treatment
• 40% incidence of lymphomas in males after 4OHT treatment
• lymphomas mainly arise from the thymus and mesenteric lymph nodes
• all lymphomas are derived from CD3+ T-cells with either a mature appearance of small lymphocytes or large lymphoblasts
• 35% of males develop intestinal cancer after 4OHT treatment, arising from the colorectum and small intestine
• 20% of males develop prostate cancer after 4OHT treatment (J:130367)
• prostate intraepithelial neoplasm (PIN) is observed at 4-6 weeks post 4-OHT treatment (J:130367)

digestive/alimentary system
• males develop small or large intestinal polyps at more than 35 weeks post 4OHT treatment

endocrine/exocrine glands
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment (J:130367)

reproductive system
• prostate hyperplasia is observed at 4-6 weeks post 4-OHT treatment (J:130367)
• most females develop endometrial hyperplasia at between 7 and 9 weeks post 4-OHT treatment (J:130367)

integument
• 10% of males and 15.4% of females develop squamous cell carcinoma of the epidermis after 4OHT treatment

homeostasis/metabolism
• about 50% of males and females exhibit malignant tumors at 21 weeks and 10-11 weeks after 4OHT treatment, respectively


Mouse Genome Informatics
cn18
    Ptentm1Hwu/Ptentm1Hwu
Tgfbr1tm1.1Karl/Tgfbr1tm1.1Karl
Tg(KRT14-cre/ERT)20Efu/0

involves: 129 * 129S4/SvJae * C57BL/6 * CD-1 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck tumors; papillomas progress to squamous cell carcinoma in the head and neck and oral cavity (J:194652)
• treatment with rapamycin 2 weeks after tamoxifen administration delays initiation and reduces progression of papilloma and onset of squamous cell carcinoma (J:194652)
• rapamycin treatment of mice with already established head and neck squamous cell carcinoma results in regression of those tumors; rapamycin decreases cell proliferation and increases apoptosis in these tumors (J:194652)
• anal neoplasms that develop in tamoxifen treated mice originate from squamous epithelia and not from columnar epithelia, indicating squamous cell carcinoma (J:209026)
• invasion into adjacent muscle tissue is seen in some mice (J:209026)
• anal squamous cell carcinoma shows increased levels of proinflammatory cytokines (J:209026)
• all mice develop head and neck squamous cell carcinomas 16 weeks after tamoxifen induction (J:209026)
• rapamycin treatment 2 weeks after tamoxifen administration decreases cell proliferation, and delays and reduces the progression of anal squamous cell carcinoma (J:209026)
• tamoxifen treated mutants to induce cre-mediated deletion of Tgfbr1 and Pten develop head and neck and oral cavity papillomas that progress to squamous cell carcinoma
• 33% of mice develop visible anal tumors in 6 weeks after tamoxifen treatment

digestive/alimentary system
• 4 weeks after oral tamoxifen treatment for 5 consecutive days, hyperplasia is seen in the perianal areas


Mouse Genome Informatics
cn19
    Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0

involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants develop tumors between 12 to 20 weeks, with 100% penetrance at 20 weeks (J:142106)
• all mice develop invasive adenocarcinoma in all prostate lobes (J:142106)
• malignant cells invade through the basement membrane into the adjacent stroma, inducing both an inflammatory and a desmoplastic response, resulting in growth of fibrous and connective tissue around the tumor (J:142106)
• mice develop prostate intraepithelial neoplasias (J:138565)

reproductive system


Mouse Genome Informatics
cn20
    Hspa5tm1Alee/Hspa5tm1.1Alee
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?

involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• mice do not develop detectable cancerous or precancerous lesions in the prostate (J:142106)


Mouse Genome Informatics
cn21
    Hspa5tm1Alee/Hspa5tm1Alee
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?

involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• mice do not develop detectable cancerous or precancerous lesions in the prostate (J:142106)


Mouse Genome Informatics
cn22
    Hspa5tm1Alee/Hspa5+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/?

involves: 129 * 129S4/SvJae * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants exhibit visible solid tumor mass with invasive adenocarcinoma in the anterior prostate, while the dorsolateral prostate and ventral prostate lobes keep their ductual structure, albeit with enlarged ducts (J:142106)
• dorsolateral prostate and ventral prostate exhibit diffusive prostate intraepithelial neoplasia (PIN) with intact basement membrane (J:142106)


Mouse Genome Informatics
cn23
    Ptentm1Hwu/Ptentm1Hwu
Tg(SFTPC-rtTA)5Jaw/0
Tg(tetO-cre)1Jaw/0

involves: 129 * 129S4/SvJae * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• doxycyline treated mice exhibit an increase in proliferation of epithelial cells lining conducting airways
• papillary epithelial hyperplasia is seen as early as 4-6 weeks of age in mice treated with doxycycline
• papillary epithelial hyperplasia is characterized by a hypercellular epithelium lining papillae with fibrovascular cores that protrude into the airway lumens
• doxycyline treated mice exhibit an increase in proliferation of nonciliated bronchial and bronchiolar Clara cells
• mice treated with doxycycline exhibit bronchiolar epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells
• mice treated with doxycycline exhibit bronchial epithelial hyperplasia, producing papillae composed of fibrovascular cores lined by a hypercellular epithelium protruding into the airway lumens consisting of enlarged cells

endocrine/exocrine glands
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity

nervous system
• pulmonary neuroepithelial cell hyperplasia, with a 2-fold increase in the number of pulmonary neuroendocrine cells in mice treated with doxycycline
• however normal respiratory epithelial cell differentiation and respiratory epithelial cell polarity

tumorigenesis
N
• overt pulmonary tumors are not observed in doxycycline treated mice at 6 weeks of age (J:146355)


Mouse Genome Informatics
cn24
    Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Brn/Trp53tm1Brn

involves: 129 * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• impaired survival is seen beginning around 2 months of age
• death appears to result from excessive bleeding due to invasion of uterine blood vessels by tumor cells

reproductive system
• by P10, luminal and glandular epithelial hyperplasia are seen (J:139053)
• enlarged relative to conditional mutants that are wild type for Trp53 (J:139053)

tumorigenesis
• hyperplasia progresses to carcinoma by 3 weeks of age (J:139053)

Mouse Models of Human Disease
OMIM IDRef(s)
Endometrial Cancer 608089 J:139053


Mouse Genome Informatics
cn25
    Gt(ROSA)26Sortm2Thl/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
Tyrc-Brd/Tyrc-Brd

involves: 129/Sv * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival is 85 days following injection of PDGF and cre compared with 27 days for similarly treated Ptentm1Hwu Trp53tm1Thl double homozygotes

tumorigenesis
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells


Mouse Genome Informatics
cn26
    Gt(ROSA)26Sortm2Thl/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Thl/Trp53tm1Thl
Tyrc-Brd/Tyrc-Brd

involves: 129/Sv * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival is 27 days following injection of PDGF and cre compared with 85 days for similarly treated Ptentm1Hwu homozygotes

tumorigenesis
• following injection of PDGF and cre, tumor growth is increased compared to in similarly treated Ptentm1Hwu homozygotes
• following injection of PDGF and cre, all mice develop glioblastoma composed of oligodendrocyte progenitor cells


Mouse Genome Informatics
cn27
    Cdkn2atm1Rdp/Cdkn2atm1Rdp
Col1a1tm1(CAG-EGFR)Char/Col1a1tm1(CAG-EGFR)Char
Ptentm1Hwu/Ptentm1Hwu

involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 10% of mice die from glioblastoma multiforme development following intracranial injection of an adenoviral cre unlike similarly treated Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors

tumorigenesis
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with a greater than 90% tumor-free survival past 30 weeks unlike similarly treated Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors

Mouse Models of Human Disease
OMIM IDRef(s)
Glioma Susceptibility 2; GLM2 613028 J:146494


Mouse Genome Informatics
cn28
    Cdkn2atm1Rdp/Cdkn2atm1Rdp
Col1a1tm2(CAG-EGFR*)Char/Col1a1tm2(CAG-EGFR*)Char
Ptentm1Hwu/Ptentm1Hwu

involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no mice surviving tumor-free beyond 10 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1tm2(CAG-EGFR*)Char homozygotes that do not develop tumors

tumorigenesis
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 10 weeks unlike similarly treated Col1a1tm2(CAG-EGFR*)Char homozygotes that do not develop tumors

Mouse Models of Human Disease
OMIM IDRef(s)
Glioma Susceptibility 2; GLM2 613028 J:146494


Mouse Genome Informatics
cn29
    Cdkn2atm1Rdp/Cdkn2atm1Rdp
Col1a1tm1(CAG-EGFR)Char/Col1a1tm2(CAG-EGFR*)Char
Ptentm1Hwu/Ptentm1Hwu

involves: 129/Sv * 129S4/SvJae * C57BL/6 * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no mice surviving tumor-free beyond 15 weeks following intracranial injection of an adenoviral cre unlike similarly treated Col1a1tm2(CAG-EGFR*)Char or Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors

tumorigenesis
• following intracranial injection of an adenoviral cre, mice develop glioblastoma multiforme with no mice surviving tumor-free beyond 13 weeks unlike similarly treated Col1a1tm2(CAG-EGFR*)Char or Col1a1tm1(CAG-EGFR)Char homozygotes that do not develop tumors

Mouse Models of Human Disease
OMIM IDRef(s)
Glioma Susceptibility 2; GLM2 613028 J:146494


Mouse Genome Informatics
cn30
    Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
• expansion of the B1 cell population
• expansion of the MZ B cell compartment
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
• cultured B cells show increased apoptosis
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor (J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages (J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2 (J:155314)
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
• decrease in IgG after TNP-OVA immunization
• increase in IgM after TNP-OVA immunization

immune system
• increase in the absolute number of splenic B cells, attributed mainly to the expansion/accumulation of MZ B cells
• expansion of the B1 cell population
• expansion of the MZ B cell compartment
• bone marrow cultured with IL-7 over a 6 day period to promote selective expansion of pre-B cells exhibits an approximate 7-fold enhancement in the frequency of activated immature mutant B cells relative to immature wild-type B cells
• gating on activated B cells shows that immature mutant B cells proliferate to a much greater extent than immature wild-type B cells
• these experiments show that upon BCR engagement, immature B cells are activated and proliferate rather than being inhibited and undergoing anergy
• increase in numbers of IgMhi antibody secreting cells and decrease in numbers of IgGhi antibody secreting cells
• reduction in germinal center formation in response to sheep red blood cell immunization and in response to environmental antigens
• B cells are responsive to chemotactic stimuli but show reduced directed movement toward the stimulus
• cultured B cells show increased apoptosis
• B cells are hyperproliferative in response to mitogenic stimuli and exhibit a lower threshold for activation through the B cell antigen receptor (J:83213)
• B cells exhibit altered cell cycle progression, with an increase in the percentage of cells in S and G2-M stages (J:83213)
• neonatal B cells proliferate strongly in response to both LPS and anti-IgM F(ab')2 unlike wild-type B cells which show a modest proliferation in response to LPS and no proliferation in response to the anti-IgM F(ab')2 (J:155314)
• impaired class-switch recombination in antibody secreting cells in response to a T-dependent antigen; B cells fail to undergo class-switch recombination to IgG3 or IgG1 in the presence of LPS or LPS plus IL-4, respectively
• however, well-formed germinal centers are observed in spleen after immunization
• decrease in IgG after TNP-OVA immunization
• increase in IgM after TNP-OVA immunization

cellular
• cultured B cells show increased apoptosis


Mouse Genome Informatics
cn31
    Cd19tm1(cre)Cgn/Cd19tm1(cre)Cgn
Ptentm1Hwu/Ptentm1Hwu

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
N
• the population of B1 and MZ B cells that are absent in single homozygous CD19 mutants is restored (J:83213)
• mutants are capable of forming germinal centers when immunized with sheep red blood cells (J:83213)


Mouse Genome Informatics
cn32
    Ptentm1Hwu/Ptentm1Hwu
Lyz2tm1(cre)Ifo/Lyz2+

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• macrophage recruitment to inflamed lungs is increased
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
• neutrophils isolated from bone marrow live longer than wild-type neutrophils (J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8 (J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice (J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils (J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils (J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a (J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils (J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice (J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice (J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia (J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia (J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production (J:148947)
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls
• induction of neutropenia in mutants with the chemotherapeutic drug, cyclophosphamide, results in enhanced neutrophil accumulation in the lungs leading to better clearance of instilled bacteria and accelerated resolution of bacteria-induced lung inflammation
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
• mutants intratracheally infected with E.coli exhibit increased neutrophil recruitment to lungs and increased lung inflammation, pulmonary edema, and increased susceptibility to death compared to controls
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice

hematopoietic system
• macrophage recruitment to inflamed lungs is increased
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
• neutrophils isolated from bone marrow live longer than wild-type neutrophils (J:114699)
• neutrophils exhibit enhanced ruffling in response to the chemoattractant fMLP or IL-8 (J:145331)
• polarized neutrophils exhibit a considerable increase in multiple pseudopodia compared to wild-type mice (J:145331)
• neutrophils show more diffuse F-actin localization at the leading edge or pseudopodia than wild-type neutrophils (J:145331)
• fMLP-stimulated, but not PMA-stimulated, neutrophils exhibit increased and prolonged superoxide production compared to wild-type neutrophils (J:145331)
• neutrophils exhibit enhanced transwell chemotaxis toward fMLP, IL-8 or C5a (J:145331)
• neutrophils are more active and move faster than wild-type neutrophils but lack some of the directionality of wild-type neutrophils (J:145331)
• in a model of peritonitis, neutrophil recruitment at sites of inflammation is increased in mutants compared to wild-type mice (J:145331)
• in a model of bacterial pneumonia, apoptosis of lung recruited neutrophils is reduced in mutants compared to wild-type mice (J:148947)
• neutrophils exhibit enhanced bacteria-killing capacity in a model of bacterial pneumonia (J:148947)
• neutrophils have an increased phagocytic index compared to wild-type in a model of bacterial pneumonia (J:148947)
• neutrophils exhibit enhanced E.coli and zymosan-induced phagocytosis-associated superoxide production (J:148947)
• in a bacterial pneumonia model in which mutants are intratracheally infected with E.coli to induce lung inflammation, mutants exhibit an increase in bacteria-induced neutrophil recruitment compared to controls
• mutants treated with the chemotherapeutic drug, cyclophosphamide, to induce neutropenia, exhibit fewer neutrophils in the lungs than untreated mutants, but more neutrophils than drug treated wild-type mice

homeostasis/metabolism
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
• increase in cytokine/chemokine concentrations in inflamed lungs of E.coli infected mutants due to increased numbers of resident alveolar macrophages and not due to enhanced capability of macrophages to produce cytokines or chemokines

mortality/aging
• mutants made neutropenic with the chemotherapeutic drug, cyclophosphamide, exhibit decreased mortality after E.coli challenge compared to wild-type mice due to enhanced neutrophil accumulation in the lungs (50% survival for mutants compared to 7% survival for wild-type mice)
• mutants exhibit an increase in pneumonia-associated death rate compared to wild-type mice, with only 50% of mutants surviving compared to 80% survival of wild-type mice

respiratory system
• number of resident alveolar macrophages in unchallenged mutants is increased by more than 60% percent compared to wild-type
• increased neutrophil recruitment to lungs leads to pulmonary edema formation and increased protein accumulation
• mutants develop more severe lung inflammation in response to bacterial pneumonia than controls

cellular
• macrophage recruitment to inflamed lungs is increased


Mouse Genome Informatics
cn33
    Cd19tm1(cre)Cgn/Cd19+
Inpp5dtm1Rav/Inpp5dtm1Rav
Ptentm1Hwu/Ptentm1Hwu

involves: 129P2/OlaHsd * 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• mutants exhibit a hunched posture by 4 months of age
• mutants exhibit lethargy by 4 months of age

growth/size
• mutants exhibit weight loss by 4 months of age

hematopoietic system
• CD19+ B cells are larger than B cells from wild-type mice
• B cell neoplasia
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
• mutants exhibit splenomegaly by 4 months of age
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
• B cells exhibit enhanced survival
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

immune system
• CD19+ B cells are larger than B cells from wild-type mice
• B cell neoplasia
• reduction in the frequency of B cells in asymptomatic double mutant mice as compared to controls or either single mutant mouse
• mutants older than 6 months of age have a 3-fold increase in the percentage of recirculating B cells in the blood, concurrent with onset of disease
• tissues containing the expanded B cell population also display an expansion of CD11b+ myeloid cells
• mutants exhibit splenomegaly by 4 months of age
• spleens of mutants over 6 months of age exhibit an expansion of CD19+ B cells, resulting in enlarged white pulp areas that often infiltrate and compress the red pulp
• B cells exhibit enhanced survival
• B cells proliferate to the prosurvival factor B cell activating factor (BAFF) while wild-type B cells do not
• B cells show a more robust proliferative response to LPS or anti-CD40 than wild-type mice

integument
• mutants exhibit ruffled fur by 4 months of age

mortality/aging
• severe morbidity and death occurs in all mutants by 1 year of age

tumorigenesis
• mutants develop marginal zone lymphoma, and less frequently, follicular B cell lymphoma or centroblastic lymphoma
• mutants develop spontaneous and lethal mature B cell neoplasms consistent with marginal zone lymphoma
• lymphoma infiltrates are seen in nonlymphoid tissues, including liver, lung, heart, and kidney


Mouse Genome Informatics
cn34
    Braftm1Mmcm/Braftm1Mmcm
Nkx3-1tm4(cre/ERT2)Mms/Nkx3-1+
Ptentm1Hwu/Pten+

involves: 129P2/OlaHsd * 129S4/SvJae * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mutants develop lethal prostate cancer 4 months after tamoxifen induction (J:191327)

tumorigenesis
• metastases to lungs and lymph nodes are seen in tamoxifen treated mutants and disseminated tumor cells are seen in the bone marrow (J:191327)
• mutants develop lethal prostate cancer 4 months after tamoxifen induction (J:191327)
• tumors are large and highly proliferative and are primarily composed of luminal epithelial cells (J:191327)
• tamoxifen treated mutants do not display significant tumor regression at 2 weeks following castration, indicating that tumors are resistant to castration (J:191327)
• tumors from tamoxifen treated mutants show absence of cellular senescence and are highly proliferative (J:191327)
• treatment of tamoxifen treated mutants with a combination of rapamycin and PD0325901 (a mitogen-activated protein/extracellular signal-regulated kinase inhibitor) results in a reduction in tumor weight, growth, and proliferation (J:191327)
• tamoxifen treated mutants develop invasive adenocarcinoma by 2-3 months after tamoxifen induction (J:191327)
• tamoxifen treated mutants display prostate intraepithelial neoplasia (PIN) by 2-4 weeks after tamoxifen induction (J:191327)

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:191327


Mouse Genome Informatics
cn35
    Cd19tm1(cre)Cgn/Cd19+
Ptentm1Hwu/Ptentm1Hwu
Tg(IghelMD4)4Ccg/0
Tg(ML5sHEL)5Ccg/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• failed tolerance induction resulting in abundant autoantibody production, indicating that B cells are prevented from acquiring an anergic state
• B cells have about 10 fold lower bound HEL than in mutants with intact Pten, suggesting that receptor occupancy is reduced on mutant autoreactive B cells and that less HEL is available in adults for inducing and sustaining anergy
• increasing the concentration of free self-antigen confers an anergic phenotype on mutant B cells, but they remain long-lived


Mouse Genome Informatics
cn36
    Ptentm1Hwu/Ptentm1Hwu
Rps6kb1tm1Gtho/Rps6kb1tm1Gtho
Tg(Mx1-cre)1Cgn/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
• mice injected with pIpC to induce Pten deletion have an enlarged spleen

tumorigenesis
• mice injected with pIpC to induce Pten deletion, develop myeloproliferative disease and T-cell acute lymphoblastic leukemia, but at a slower rate than in single Pten mutants

mortality/aging
• mean survival time of mice injected with pIpC to induce Pten deletion is 46 days

immune system
• mice injected with pIpC to induce Pten deletion have an enlarged thymus
• mice injected with pIpC to induce Pten deletion have an enlarged spleen

endocrine/exocrine glands
• mice injected with pIpC to induce Pten deletion have an enlarged thymus


Mouse Genome Informatics
cn37
    Akt2tm1.1Mbb/Akt2tm1.1Mbb
Ptentm1Hwu/Ptentm1Hwu
Tg(Alb-cre)21Mgn/0

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
• about 25-30% increase in fasting glucose levels at 1 month of age
• glucose intolerance

liver/biliary system
N
• the liver phenotype observed in single Pten mutants is significantly reduced, with liver weights, triglyceride levels in the liver and fatty liver almost similar to controls (J:160759)


Mouse Genome Informatics
cn38
    Ptentm1Hwu/Ptentm1Hwu
Trp53tm1Brn/Trp53tm1Brn

involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6 * FVB
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice treated with an adenovirus expressing cre die by 6 months of age

tumorigenesis
• urinary bladder tumors in Adeno-cre treated mice are of epithelial origins and exhibit features of carcinoma in situ and high-grade invasive carcinoma with areas of transitional cell, squamous, and sarcomatoid carcinoma
• by 6 months, all mice treated with an adenovirus expressing cre (Adeno-cre) develop large urinary bladder tumors unlike wild-type mice
• by 4 to 6 months, 60% of Adeno-cre treated mice exhibit metastasis in the local lymph nodes, spleen, liver, and diaphragm
• however, treatment of mice with rapamycin following Adeno-cre injection prevents urinary bladder tumor formation

Mouse Models of Human Disease
OMIM IDRef(s)
Bladder Cancer 109800 J:146760


Mouse Genome Informatics
cn39
    Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Tg(GFAP-cre)25Mes/0
Trp53tm1Tyj/Trp53+

involves: 129S1/Sv * 129S2/SvPas * 129S4/SvJae * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological
• exaggerated startle response
• ataxic gait
• generalized motor seizures

nervous system
• generalized motor seizures

tumorigenesis
• gliomas from asymptomatic mutants are primarily classified as grade 3 astocytomas
• 5-fold higher growth rate of astrocytomas compared with tumors from transgenic mice heterozygous for Nf1tm1Par and Trp53tm1Tyj and hemizygous for Tg(GFAP-cre)25Mes


Mouse Genome Informatics
cn40
    Ptentm1Hwu/Ptentm1Hwu
Tg(CAG-Bgeo/ALPP)1Lbe/0
Tg(Ela1-cre/ERT)1Dam/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
N
• 4 weeks after tamoxifen injections to induce Cre expression, pancreata exhibit no ductal metaplasia (J:102226)


Mouse Genome Informatics
cn41
    Ptentm1Hwu/Ptentm1Hwu
Cnptm1(cre)Kan/Cnp+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

digestive/alimentary system
• mutants develop megacolon later in life
• mutants develop hyperplasia of the salivary glands later in life

endocrine/exocrine glands
• mutants develop hyperplasia of the salivary glands later in life

nervous system
• increase in white matter volume
• progressive enlargement of all white matter tracts
• myelinated axons of the corpus callosum that intermingle with glial cells are in disarray
• density of myelinated axons in the ventral corpus callosum is decreased by 36.6% at 3 months of age
• oligodendroglial hypertrophy is seen at 4 months of age
• increase in numbers of myelinating and nonmyelinating Schwann cells
• increase in myelin sheath thickness
• sciatic nerves are increased in size
• myelinated axons are more loosely spaced in sciatic nerves
• number of myelinated axons in the sciatic nerve is higher at 3 months of age; increase in myelination is primarily for small caliber axons
• hypermyelination in both white and gray matter
• hypermyelination is primarily a consequence of additional membrane wraps and not by altered ultrastructure
• increase in myelin thickness is seen for axons of all calibers, however not all fibers are visibly hypermyelinated
• however, do not see ectopic myelination of CNS axons that normally are unmyelinated
• normally nonmyelinated C-fiber axons are spirally enwrapped by Remak Schwann cells; up to 10 membrane layers per axon are seen resulting in non compacted myelin
• Remak Schwann cells also ensheath bundles of collagen fibrils
• myelin outfoldings of variable length and aberrant myelin depositions are seen in the corpus callosum

vision/eye
• mutants develop cataracts later in life

reproductive system
• poor breeding


Mouse Genome Informatics
cn42
    Ptentm1Hwu/Ptentm1Hwu
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
normal phenotype
• mice are viable and exhibit not visible abnormalities and remain healthy throughout 12 months of study, with normal lungs


Mouse Genome Informatics
cn43
    Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Scgb1a1tm1.1(cre)Fjd/Scgb1a1+

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean survival is 8 weeks

immune system
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression

respiratory system
• increase in inflammation in lesions compared to single Kras mutants, with an increase in neutrophil and endothelial cell infiltration; infiltration of these cells increases with malignant progression
• by 2 months of age, mutants exhibit tachypnea

tumorigenesis
• mutants have higher numbers of lesions and more extensive tumors than single Kras mutants
• mutants develop distinct bronchial and alveolar tumors
• mutants develop lung lesions as early as 4 weeks of age including proliferative atypical adenomatous hyperplasia lesions
• mutants develop lung lesions as early as 4 weeks of age that includes atypical papillary bronchiolar proliferation
• mucinous bronchioloalveolar cell carcinoma-like lesions, a subtype of lung adenocarcinoma

growth/size
• by 2 months of age, mutants exhibit weight loss


Mouse Genome Informatics
cn44
    Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• proliferation is increased in the endothelium epithelium (J:162027)
• increase in uterine weight at 2 weeks of age (J:162027)

tumorigenesis
• mutants develop endometrial cancer (J:162027)
• mutants exhibit endometrial hyperplasia at 4 weeks of age and develop endometrial adenocarcinoma with invasion into the myometrium at 2 months of age (J:162027)


Mouse Genome Informatics
cn45
    Errfi1tm1Jwj/Errfi1tm1Jwj
Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival time of double mutants is shorter than either single mutant, with mice dying by 16 weeks of age

reproductive system
• decrease in the number of apoptotic cells in the endothelium epithelium compared to single Pten mutants (J:162027)
• proliferation is increased in the endothelium epithelium (J:162027)
• mutants exhibit endometrial hyperplasia at 2 weeks of age and develop endometrial adenocarcinoma at 4 weeks of age (J:162027)
• however, myometrial hyperplasia is not observed in the uteri of mutants (J:162027)
• increase in uterine weight at 2 weeks of age, with weight at 4 weeks greater than in single Pten mutants (J:162027)

tumorigenesis
• mutants exhibit distant metastases into the ovary, diaphragmatic skeletal muscle, lymph node, colon and pancreas
• development of endometrial cancer is accelerated compared to either single mutant (J:162027)

Mouse Models of Human Disease
OMIM IDRef(s)
Endometrial Cancer 608089 J:162027


Mouse Genome Informatics
cn46
    Ctnnb1tm2Kem/Ctnnb1tm2Kem
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• embryonic lethal


Mouse Genome Informatics
cn47
    Ctnnb1tm2Kem/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• die before P68 with vascular complications

hematopoietic system
• 100% of mutants develop myeloproliferative disorder at about P30

cardiovascular system
• mutants exhibit vascular complication


Mouse Genome Informatics
cn48
    Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Tg(Gfap-cre)77.6Mvs/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * BALB/c * C57BL/6NHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
N
• mutants do not develop tumors (J:154673)


Mouse Genome Informatics
cn49
    Pgrtm2(cre)Lyd/Pgr+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• impaired survival is seen beginning around 5 months of age

reproductive system
• by P10, luminal and glandular epithelial hyperplasia are seen (J:139053)

tumorigenesis
• hyperplasia progresses to carcinoma by 1 month of age with invasion into the myometrium detected by 3 months of age (J:139053)

Mouse Models of Human Disease
OMIM IDRef(s)
Endometrial Cancer 608089 J:139053


Mouse Genome Informatics
cn50
    Artm1Verh/Y
Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate (J:172730)
• cancer progression is similar to single conditional Pten mice (J:172730)
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe (J:172730)
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer (J:172730)
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer (J:172730)
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation (J:172730)

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:172730


Mouse Genome Informatics
cn51
    Erbb2tm8(Erbb2)Mul/Erbb2+
Ptentm1Hwu/Pten+
Tg(MMTV-cre)7Mul/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 35% incidence of lung metastases compared with 5% in single Erbb2 mutants
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 6.5 compared with 15.3 months
• tumor progression is associated with loss of heterozygosity at the Pten locus in 50% of mutant mammary tumors
• tumors are similar to basal-like subtype of human breast cancer

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:133305


Mouse Genome Informatics
cn52
    Erbb2tm8(Erbb2)Mul/Erbb2+
Ptentm1Hwu/Ptentm1Hwu
Tg(MMTV-cre)7Mul/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mammary tumor onset is accelerated in virgin females compared with either single Pten or single Erbb2 mutants, with tumor latencies of 2.4 compared with 15.5 months
• 25% of tumors are adenomyoepitheliomas
• 25% of tumors are Erbb2 type neoplasms
• 25% of tumors exhibit squamous metaplasia and retention of myoepithelium
• 25% of tumors are glandular, composed of distinctive large cell population that are a signature phenotype of mammary tumors in these mice
• tumors are similar to HER2 and basal-like subtype of human breast cancer

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:133305


Mouse Genome Informatics
cn53
    Nf1tm1Par/Nf1+
Ptentm1Hwu/Pten+
Trp53tm1Elee/Trp53+
Tg(GFAP-cre)25Mes/0

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• most die as early as 10 weeks of age, and usually within a week of showing signs of morbidity

behavior/neurological
• exaggerated startle response
• ataxic gait
• generalized motor seizures

nervous system
• generalized motor seizures

tumorigenesis
• mutants develop astrocytomas
• neurospheres from mutant astrocytomas exhibit loss of heterozygosity at both Nf1 and Trp53 loci


Mouse Genome Informatics
cn54
    Bcl2l11tm1.1Ast/Bcl2l11+
Ptentm1Hwu/Pten+
Tg(CD2-cre)4Kio/0

involves: 129S1/Sv * 129S4/SvJae * C57BL/10 * CBA/Ca
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice

hematopoietic system
• at 20 to 28 weeks of age, mice exhibit increased germinal center B cell number compared to controls but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice
• at 20 to 28 weeks of age, mice accumulate more antigen-experienced T cells than in control mice but not as much as in Gt(ROSA)26Sortm3Rsky/Gt(ROSA)26Sortm3Rsky/ Tg(CD2-cre)1Kio mice


Mouse Genome Informatics
cn55
    Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre)89.1Dam/0
Trp53tm1Tyj/Trp53tm1Tyj

involves: 129S2/SvPas * 129S4/SvJae * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• 1 of 5 mutants develop a small acinar carcinoma
• 2 of 5 mutants develop papillary adenocarcionomas at 4 and 6 months of age


Mouse Genome Informatics
cn56
    Cdkn1atm1Tyj/Cdkn1atm1Tyj
Ptentm1Hwu/Ptentm1Hwu
Tg(Fabp1-cre)1Jig/0

involves: 129S2/SvPas * 129S4/SvJae * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• bladder urothelium exhibits increased cell proliferation

tumorigenesis


Mouse Genome Informatics
cn57
    Ptentm1Hwu/Ptentm1Hwu
Tg(Cr2-cre)3Cgn/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• no time point given


Mouse Genome Informatics
cn58
    Ptentm1Hwu/Ptentm1Hwu
Tg(Fabp4-cre)1Abel/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
adipose tissue
N
• no differences in body weight and fat storage (J:97588)

homeostasis/metabolism
• fasting mutants exhibit a 2.1-fold decrease in plasma insulin levels compared to controls indicating enhanced insulin sensitivity
• during a glucose tolerance test, mutants show a blunted elevation of blood glucose; the mean peak increase in blood glucose is 19% lower than that of controls
• mutants are protected from developing streptozotocin-induced diabetes; they maintain normal glycemia and remain resistant to the development of hyperglycemia
• mutants are more sensitive to insulin challenge (in insulin tolerance test), showing a 24% lower blood glucose at 60 min compared to wild-type mice
• insulin resistance is 1.9-fold lower for mutants than controls
• 36% lower serum concentrations of the adipocytokine resistin

immune system
• 36% lower serum concentrations of the adipocytokine resistin


Mouse Genome Informatics
cn59
    Ptentm1Hwu/Ptentm1Hwu
Tg(CYP19A1-cre)1Jri/0

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• the increased numbers of corpora lutea are at different stages of differentiation than in controls (J:138315)
• luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice (J:138315)
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active (J:138315)
• after 3 months of age, ovaries contain increased numbers of corpora lutea (J:138315)
• females exhibit increased follicle growth (J:138315)
• numbers of apoptotic follicles decreased in eCG-primed mutant ovaries (J:138315)
• granulosa cells exhibit increased proliferation (J:138315)
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries (J:138315)
• after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea (J:138315)

reproductive system
• the increased numbers of corpora lutea are at different stages of differentiation than in controls (J:138315)
• luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice (J:138315)
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active (J:138315)
• after 3 months of age, ovaries contain increased numbers of corpora lutea (J:138315)
• females exhibit increased follicle growth (J:138315)
• numbers of apoptotic follicles decreased in eCG-primed mutant ovaries (J:138315)
• granulosa cells exhibit increased proliferation (J:138315)
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries (J:138315)
• after 3 months of age, ovaries are larger and contain increased numbers of corpora lutea (J:138315)
• immature females primed with a superovulatory regiment of equine chorionic gonadotropin (eCG), followed by human CG, ovulate more oocytes than control mice, indicating advanced ovulation rate and increased ovulation (J:138315)
• females give birth to approximately 20% more pups than controls during a 6-month breeding period

tumorigenesis
N
• females do not develop ovarian tumors (J:138315)

cellular
• granulosa cells exhibit increased proliferation (J:138315)
• numbers of cleaved caspase 3 (CC3)-positive granulosa cells are decreased in eCG-primed mutant ovaries (J:138315)
• the increased numbers of corpora lutea are at different stages of differentiation than in controls (J:138315)
• luteolysis is dramatically impaired and delayed in mutants on a superovulatory regimen of eCG/hCG compared to wild-type mice (J:138315)
• steroid biosynthesis is similar in mutants as in controls indicating that even though life span of corpora lutea are extended, they do not remain steroidogenically active (J:138315)


Mouse Genome Informatics
cn60
    Amhr2tm3(cre)Bhr/Amhr2+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• most females lack ovarian abnormalities (J:142150)
• many females fail to carry pregnancies to term (J:142150)
• many females have small litters due to fetal death after E9.5

tumorigenesis
• ganulosa cell tumors are aggressive and metastasize to the lungs
• 5 of 70 females developed ovarian tumors (J:142150)
• ovarian tumors are granulosa cell tumors (J:142150)


Mouse Genome Informatics
cn61
    Fastm1Ach/Fastm1Ach
Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• triple mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination are protected from developing ovarian cancer, with only 1 of 11 mice developing cancer compared to 9 of 12 double Kras and Pten mutants


Mouse Genome Informatics
cn62
    Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants injected with an adenoviral Cre into the right ovarian bursa to induce recombination develop ovarian cancer eight weeks after injection (J:161953)

Mouse Models of Human Disease
OMIM IDRef(s)
Ovarian Cancer 167000 J:161953


Mouse Genome Informatics
cn63
    Ptentm1Hwu/Ptentm1Hwu
Rictortm1.1Mgn/Rictortm1.1Mgn

involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• prostatic ductules of mutants infected with an adenovirus expressing Cre recombinase exhibit a mixed phenotype containing mostly normal, organized epithelial cells and patches of large, disorganized hyperplastic cells; inefficient deletion of Rictor is seen in the patches of disorganized hyperplastic cells (J:144810)
• prostate tissue histology of mutants infected with an adenovirus expressing Cre recombinase appears normal except that epithelial cells are slightly smaller (J:144810)

reproductive system
• prostatic ductules of mutants infected with an adenovirus expressing Cre recombinase exhibit a mixed phenotype containing mostly normal, organized epithelial cells and patches of large, disorganized hyperplastic cells; inefficient deletion of Rictor is seen in the patches of disorganized hyperplastic cells (J:144810)
• prostate tissue histology of mutants infected with an adenovirus expressing Cre recombinase appears normal except that epithelial cells are slightly smaller (J:144810)

tumorigenesis
• mutants infected with an adenovirus expressing Cre recombinase do not develop prostate adenocarcinoma


Mouse Genome Informatics
cn64
    Ptentm1Hwu/Ptentm1Hwu
Rictortm1.1Mgn/Rictortm1.1Mgn
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * 129S6/SvEvTac * BALB/c * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• average beta cell size is increased by 31% compared to controls and by 15% compared to single conditional Pten mutants
• however, mutants show normal beta cell proliferation
• beta cell mass is about 40% lower than that of single conditional Pten mutants

growth/size

homeostasis/metabolism
• total glucose excursion is lower compared to single conditional Rictor mutants
• fed blood glucose concentration remains similar to the controls, however mutants show a lower blood glucose concentration at 30 and 60 min after an intraperitoneal glucose bolus compared to single conditional Rictor mutants
• mutants exhibit lower plasma insulin levels 15 min after glucose challenge and lower total insulin output compared with controls
• however, insulin secretion by glucose stimulated islets is similar to controls and pancreatic insulin content is unchanged


Mouse Genome Informatics
cn65
    Nkx3-1tm4(cre/ERT2)Mms/Nkx3-1+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)
• castrated male mice show rapid formation of high-grade PIN and carcinoma after androgen-mediated prostate regeneration with evidence of microinvasion (J:153425)
• mutants show extensive prostate intraepithelial neoplasia (PIN) III and PIN IV 9-12 months after tamoxifen induction, with some areas of squamous papilloma, however mutants rarely develop lethal prostate cancer up to 2 years following tamoxifen induction (J:191327)


Mouse Genome Informatics
cn66
    Ptentm1Hwu/Ptentm1Hwu
Smad4tm2.1Cxd/Smad4tm2.1Cxd
Tg(Alb1-cre)1Dlr/0

involves: 129S4/SvJae * 129S6/SvEvTac * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mutants die before 10 months of age

endocrine/exocrine glands
• increase in branching of bile ducts in the liver

liver/biliary system
• increase in branching of bile ducts in the liver
• increase in liver size and weight due to fat accumulation in the liver

tumorigenesis
• at 2 months of age, hyperplastic foci emerge from bile ducts and continue to grow, leading to tumor formation in all mice at 4-7 months of age; tumors are intrahepatic cholangiocellular carcinoma


Mouse Genome Informatics
cn67
    Amhr2tm3(cre)Bhr/Amhr2+
Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• metastasis is not observed, but this might be that mice do not have sufficient time to develop metastasis due to early lethality, however, when granulosa cell tumors are removed at 6 weeks of age, mice show development of large lung metastases 6-16 weeks later, indicating that tumors indeed are metastatic (J:142150)
• 44% of mice develop pulmonary metastases by 4 months (J:149060)
• presence of nests of dysplastic cells are seen in the ovaries of newborn mice and E20.5, but not E18.5, indicating that tumor growth begins perinatally (J:142150)
• females develop ovarian granulosa cell bilateral tumors with 100% penetrance from an early age
• 100% penetrance of aggressive testicular cancer (J:149060)
• tumors are first observable at 5 weeks of age, and by 3 months of age, about 70% of mice have unilateral testicular tumors and 30% have bilateral tumors (J:149060)
• tumors exhibit characteristics of granulosa cell tumors of the testis and not Sertoli cell tumors (J:149060)

reproductive system
• seminiferous tubule degeneration is seen by 3 weeks of age (J:149060)

endocrine/exocrine glands
• seminiferous tubule degeneration is seen by 3 weeks of age (J:149060)

cardiovascular system
• pulmonary tumor cell embolisms

hematopoietic system
• severe anemia
• extrensive extramedullary hematopoiesis

mortality/aging
• female mice die before 9 weeks of age

respiratory system
• pulmonary tumor cell embolisms


Mouse Genome Informatics
cn68
    Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
Tg(CYP19A1-cre)1Jri/0

involves: 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mutants die within 2-3 months of age due to tumor burden

tumorigenesis
• mutants exhibit precancerous lesions in the ovaries by 3 weeks of age (J:186144)
• mutants develop large granulosa cell tumors by 6-8 weeks of age (J:186144)

endocrine/exocrine glands
• granulosa cell proliferation is increased and apoptosis is decreased in the ovaries at 5-6 weeks of age (J:186144)
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked (J:186144)

reproductive system
• granulosa cell proliferation is increased and apoptosis is decreased in the ovaries at 5-6 weeks of age (J:186144)
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked (J:186144)

homeostasis/metabolism

cellular
• marker analysis indicates that at 6 weeks of age granulosa cell differentiation is blocked (J:186144)

Mouse Models of Human Disease
OMIM IDRef(s)
Ovarian Cancer 167000 J:186144


Mouse Genome Informatics
cn69
    Amhr2tm3(cre)Bhr/Amhr2+
Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• female mutants develop granulosa cell tumors by 3 weeks of age (J:186144)
• male mutants develop testicular granulosa cell tumors by 5 weeks of age (J:186144)

Mouse Models of Human Disease
OMIM IDRef(s)
Ovarian Cancer 167000 J:186144


Mouse Genome Informatics
cn70
    Ctnnb1tm1Mmt/Ctnnb1tm1Mmt
Ptentm1Hwu/Ptentm1Hwu
Tg(Upk2-cre)6Xrw/0

involves: 129S4/SvJae * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

tumorigenesis
• mice develop urothelial bladder tumors that progress to papillary carcinoma


Mouse Genome Informatics
cn71
    Ctnnb1tm1Mmt/Ctnnb1+
Ptentm1Hwu/Ptentm1Hwu
Tg(Upk2-cre)6Xrw/0

involves: 129S4/SvJae * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging

tumorigenesis
• mice develop urothelial bladder tumors that progress to papillary carcinoma


Mouse Genome Informatics
cn72
    Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants exhibit accelerated development of acinar-to-ductal metaplasia, malignant pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma compared to single heterozygous Kras mutants, with almost 100% of mutants succumbing to cancer by 12 months of age
• 21 of 25 mice alive past 2 months of age develop well-to-moderately differentiated invasive ductal cancers
• rare metastasis to lungs is seen
• at 3 months of age, 8 of 12 mutants show development of pancreatic ductal adenocarcinoma (PDAC), and all mice show PDAC by 6 months of age
• loss of Pten heterozygosity is seen during pancreatic ductal adenocarcinoma progression but not in mPanIN lesions
• mutants show malignant pancreatic intraepithelial neoplasia (mPanIN) development starting at 1 month of age, and all show mPanIN by 3 months of age

mortality/aging
• median survival time is about 3.5 months

endocrine/exocrine glands
• acinar-to-ductal metaplasia is seen at 1-3 months of age, concentrated in the transition zone between morphologically normal pancreatic structures and mPanIN and PDAC lesions
• acinar-to-ductal metaplasia development precedes mPanIN formation
• metaplastic lesions show an increase in CD44+ cells

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:164210


Mouse Genome Informatics
cn73
    Ptentm1Hwu/Ptentm1Hwu
Tg(Nkx2-1-cre)2Sand/0

involves: 129S4/SvJae * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
homeostasis/metabolism
N
• Background Sensitivity: unlike on the congenic C57BL/6 background, mutants on the BALB/c background have normal T4 and TSH levels (J:197590)
• after naphthalene administration to induce lung injury, the proximal airway epithelium at 3 and 7 days post injury appears intact with no signs of injury
• after naphthalene administration to induce lung injury, the level of injury in the bronchial airway epithelium is reduced and repair is enhanced compared to controls

respiratory system
• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs
• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region
• lungs exhibit increased cell proliferation and decreased apoptosis
• lungs at 8 weeks of age sometimes contain a mass consisting of epithelial cells (putative progenitor cell masses) around the BADJ area; masses are slow growing and are organized into ductlike structures
• marker analysis indicates a block in transition from precursor to terminally differentiated cell types indicating impaired epithelial cell fate determination in the lung
• increase in number of Clara cells in the lungs and a decrease in the number of ciliated cells, the terminally differentiated progeny of Clara cells
• progressive epithelial hyperplasia extending from the trachea to the small bronchioles is seen in the proximal lung epithelium from early stages of lung development and in adults

cellular
• mutants exhibit an increase in the proliferation rate of the epithelial cells in E15.5 lungs
• expansion of epithelial cell populations occurs in multiple progenitor cell niches of the lungs including the tracheal basal cells in the proximal lung, the neuroepithelial bodies (NEB) in the distal bronchi and the progenitor cells occupying the bronchioalveolarduct junction (BADJ) region

endocrine/exocrine glands
• Background Sensitivity: at P14, epithelial cell proliferation rates in the thyroid are lower on the mixed BALB/c background than on the congenic C57BL/6 background
• at P14, thyroid architecture is conserved but an increase in the number of epithelial cells along the follicles is seen, resembling a goiter disease

mortality/aging
N
• Background Sensitivity: mutants survive to adulthood on the BALB/c background without presenting any obvious pathological conditions unlike mice on the congenic C57BL/6 background (J:197590)


Mouse Genome Informatics
cn74
    Ptentm1Hwu/Pten+
Tg(Nkx2-1-cre)2Sand/0

involves: 129S4/SvJae * BALB/c * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mutants have an enlarged thyroid at 2 years of age and exhibit a goiter-like phenotype, but do not show development of tumors

homeostasis/metabolism
• P14 mutants show an increase in T4 levels


Mouse Genome Informatics
cn75
    Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Tg(Pdx1-cre)89.1Dam/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• all mutants develop pancreatic ductal adenocarcinoma by 3 weeks of age

endocrine/exocrine glands
• mutants exhibit acinar-to-ductal metaplasia
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17

homeostasis/metabolism
• pancreas at P1-P17 shows edema

mortality/aging
• mutants are moribound by weaning, with a median survival of about 17 days

digestive/alimentary system
• mutants show severe exocrine pancreatic atrophy and edema along with the presence of mPanINs, metaplasias, and ducto-insular complexes and pancreatic ductal adenocarcinoma at P17

Mouse Models of Human Disease
OMIM IDRef(s)
Pancreatic Cancer 260350 J:164210


Mouse Genome Informatics
cn76
    Ptentm1Hwu/Ptentm1Hwu
Tg(Ins2-cre)25Mgn/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• beta-cell size is increased by 15% compared to controls
• number of proliferating beta-cells is increased by 34% compared to controls
• beta-cell mass is 86% higher than controls after adjusting for body size
• however, pancreatic insulin content is unchanged and insulin sensitivity is normal

growth/size


Mouse Genome Informatics
cn77
    Ptentm1Hwu/Ptentm1Hwu
Tg(Pbsn-cre)4Prb/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 3 of 14 mice die by age 12 to 29 weeks (J:93902)
• however, all castrated mice survive from 7 to 10 months (J:93902)
• 12 month survival rate of mutants is 60% on the high-omega-3 diet, 10% on the low-omega-3 diet and 0% on the high-omega-6 diet (J:124208)
• mutants on a high-omega-6 diet do not survive beyond 10 months of age and die due to bladder obstruction by the prostate tumor compressing the urethra (J:124208)

reproductive system
• higher numbers of apoptotic cells are seen in mutant prostates from mice on the high-omega-3 diet than on the high-omega-6 diet (J:124208)
• prostate lobes are enlarged and exhibit increased vascularity and cellularity (J:124208)
• at 4 weeks, epithelium cells in the lateral prostate are larger than in Ptentm1Hwu homozygotes (J:93902)
• without cellular atypia by 4 weeks of age (J:93902)
• mice exhibit progressive enlargement of the prostate gland compared to in Ptentm1Hwu homozygotes (J:93902)
• however, castration reduces prostate size (J:93902)
• prostate weight is higher than in controls starting at 8 weeks of age (J:124208)
• prostate weight gain from 5 to 24 weeks is significantly less in mice fed a high-omega-3 diet than in mice fed a high-omega-6 diet (J:124208)
• at 4 weeks, mice develop multifocal hyperplasia compared to in Ptentm1Hwu homozygotes (J:93902)
• hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes (J:93902)
• prostate cancer cells exhibit increased proliferation compared to in Ptentm1Hwu homozygotes (J:93902)
• cancer cells induce a desmoplastic response (J:93902)
• castrated mice exhibit increased proliferation compared with similarly treated Ptentm1Hwu homozygotes (J:93902)
• cancer cells induce inflammation (J:93902)

tumorigenesis
• males develop prostate cancer (J:124208)
• mice develop invasive adenocarcinoma by 9 weeks of age in all lobes (J:93902)
• prostate cancers are metastatic (J:93902)
• castrated mice still develop invasive adenocarcinoma (J:93902)
• 80% of mutants fed a high-omega-6 diet develop invasive carcinoma while 50% of mutants fed a high-omega-3 diet develop invasive carcinoma (J:124208)
• by 6 weeks of age, all mice develop prostate intraepithelial neoplasia (J:93902)
• latency to prostate intraepithelial neoplasia is 1.5 months (J:93902)
• males develop PIN lesions after 16 months of age (J:106650)
• omega-3 polyunsaturated fatty acids (PUFAs) slow the progression of prostate tumors in 5- to 8-week old mutants; once carcinoma develops, omega-3 PUFAs induce apoptosis and decrease the growth of the tumor

immune system
• cancer cells induce inflammation (J:93902)
• mutants surviving 6 months or longer exhibit pyelonephritis

endocrine/exocrine glands
• higher numbers of apoptotic cells are seen in mutant prostates from mice on the high-omega-3 diet than on the high-omega-6 diet (J:124208)
• prostate lobes are enlarged and exhibit increased vascularity and cellularity (J:124208)
• at 4 weeks, epithelium cells in the lateral prostate are larger than in Ptentm1Hwu homozygotes (J:93902)
• without cellular atypia by 4 weeks of age (J:93902)
• mice exhibit progressive enlargement of the prostate gland compared to in Ptentm1Hwu homozygotes (J:93902)
• however, castration reduces prostate size (J:93902)
• prostate weight is higher than in controls starting at 8 weeks of age (J:124208)
• prostate weight gain from 5 to 24 weeks is significantly less in mice fed a high-omega-3 diet than in mice fed a high-omega-6 diet (J:124208)
• at 4 weeks, mice develop multifocal hyperplasia compared to in Ptentm1Hwu homozygotes (J:93902)
• hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes (J:93902)
• prostate cancer cells exhibit increased proliferation compared to in Ptentm1Hwu homozygotes (J:93902)
• cancer cells induce a desmoplastic response (J:93902)
• castrated mice exhibit increased proliferation compared with similarly treated Ptentm1Hwu homozygotes (J:93902)
• cancer cells induce inflammation (J:93902)

renal/urinary system
• mutants surviving 6 months or longer exhibit retention of urine in the anterior prostate lobes
• mutants surviving 6 months or longer exhibit pyelonephritis

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:93902


Mouse Genome Informatics
cn78
    Ptentm1Hwu/Pten+
Tg(Pbsn-cre)4Prb/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• latency to prostate intraepithelial neoplasia is 8 to 10 months (J:93902)


Mouse Genome Informatics
cn79
    Ptentm1Hwu/Pten+
Tg(ARR2/Pbsn-FGF8)3Prb/0
Tg(Pbsn-cre)4Prb/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• enlarged prostate gland due to epithelial hyperplasia (J:106650)

reproductive system
• enlarged prostate gland due to epithelial hyperplasia (J:106650)

tumorigenesis
• metastasis of adenocarcionma into lymph nodes is observed, with 50-60% penetrance
• prostatic adenocarcinomas are seen from 9 months onward (J:106650)
• adenocarcinomas are seen in all lobes, although more often in the dorsolateral and ventral lobes than anterior lobes (J:106650)
• 6 of 17 mutants at 9-16.2 months of age and 9 of 10 mutants at 18.2-19.1 months exhibit adenocarcinomas (J:106650)
• adenocarcinomas show loss of heterozygosity of Pten (J:106650)
• 2 of 31 mutants develop a rare form of mucinous adenocarcinoma (J:106650)
• males by 6.5 months of age exhibit hyperplasia and focal-low grade PIN lesions in the prostate (J:106650)
• males older than 7.5 months of age exhibit high-grade PINs (J:106650)

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:106650


Mouse Genome Informatics
cn80
    Ptentm1Hwu/Ptentm1Hwu
Tg(CAG-fat-1)1Jxk/0
Tg(Pbsn-cre)4Prb/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• mice fed a high-omega-6 diet exhibit significantly lower prostate weights than mice without Tg(CAG-fat-1)1Jxk (J:124208)

homeostasis/metabolism
• mice fed a high-omega-6 diet exhibit a much lower omega-6/omega-3 ratio in the blood and prostate than mice without the Tg(CAG-fat-1)1Jxk transgene, indicating that fat-1 is able to convert most of the omega-6 polyunsaturated fatty acids to omega-3

reproductive system
• mice fed a high-omega-6 diet exhibit significantly lower prostate weights than mice without Tg(CAG-fat-1)1Jxk (J:124208)


Mouse Genome Informatics
cn81
    Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh5-cre)7Mlia/0

involves: 129S4/SvJae * BALB/c * C57BL/6 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
hematopoietic system
• 70% of mutants exhibit enlarged thymus
• progressive development of myeloproliferative disorder and leukemogenesis in the chronic phase followed by blast crisis
• 2-3 months after birth, mutants show increased circulating neutrophils and white blood cells and leukemic blast invasion into hematopoietic and non-hematopoietic organs
• one month after birth, mutants develop a myeloid shift with increased neutrophil counts
• splenomegaly

immune system
• 70% of mutants exhibit enlarged thymus
• 2-3 months after birth, mutants show increased circulating neutrophils and white blood cells and leukemic blast invasion into hematopoietic and non-hematopoietic organs
• one month after birth, mutants develop a myeloid shift with increased neutrophil counts
• splenomegaly
• 70% of mutants exhibit enlarged lymph nodes

liver/biliary system
• hepatomegaly

tumorigenesis
• 74% of mutants develop T-lymphoblastic leukemia
• 26% of mutants develop acute myeloid leukemia

endocrine/exocrine glands
• 70% of mutants exhibit enlarged thymus


Mouse Genome Informatics
cn82
    Ptentm1Hwu/Ptentm1Hwu
Tg(Camk2a-cre)T50Stl/0
Tg(Thy1-EGFP)MJrs/0

involves: 129S4/SvJae * BALB/c * C57BL/6J * CBA
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• increase in brain size due to expansion of allocortex and neocortex
• apical dendrites of pyramidal neurons in cortical layer 2/3 but not layer 5 are longer and more tortuous than in controls
• total arbor length is on average 1.6 mm longer in mutants, indicating an approximate 80% expansion of the apical dendritic tree
• however, basal dendritic length is not different
• rapamycin treatments completely prevent dendritic growth seen following Pten deletion


Mouse Genome Informatics
cn83
    Ptentm1Hwu/Ptentm1Hwu
Vhltm1Jae/Vhltm1Jae
Tg(Cdh16-cre)91Igr/0

involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex
• 3 of 14 mice show isolated regions of benign squamous metaplasia within the kidney cortex
• kidney epithelial cells fail to maintain their primary cilia, resulting in uncontrolled proliferation and cyst formation
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
• hyperproliferation of the urothelium in the renal pelvis is more pronounced than in single Pten mutants
• males and females exhibit enlarged and heavier kidneys due to epithelial tubule cysts
• mutants develop multiple epithelial tubule cysts in the kidney cortex and medulla
• cysts develop in all mice (14 of 14) and are seen as early as 6-8 weeks of age
• cysts arise in collecting ducts and distal tubules
• most cysts are lined by a single layer of epithelial cells (simple cysts), whereas ~8% of cysts are lined by multilayered epithelial cells with occasional papillary projections (atypical cysts)
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
• mutants develop multiple epithelial tubule cysts in the kidney cortex
• mutants develop multiple epithelial tubule cysts in the kidney medulla

cellular
• mutants exhibit reduced frequency of primary cilia in cysts, with distal tubule cysts displaying only ~30% ciliated cells relative to 80-90% ciliated cells in wild-type
• cysts exhibit a 3- to 6-fold increase in the number of Ki-67-positive kidney epithelial cells per mm2 of cortex

tumorigenesis
N
• no tumors areas seen at 3-6 months of age, when mice are euthanized to avoid renal failure (J:137073)

Mouse Models of Human Disease
OMIM IDRef(s)
Von Hippel-Lindau Syndrome; VHL 193300 J:137073


Mouse Genome Informatics
cn84
    Ptentm1Hwu/Ptentm1Hwu
Tg(Cdh16-cre)91Igr/0

involves: 129S4/SvJae * BALB/c * C57BL/6J * ICR
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
renal/urinary system
N
• mutants do not develop hydronephrosis (J:137073)
• hyperproliferation and enlarged epithelial cells in the ureter
• hyperproliferation and enlarged epithelial cells in the bladder


Mouse Genome Informatics
cn85
    ApcMin/Apc+
Ptentm1Hwu/Ptentm1Hwu
Tg(Vil-cre)997Gum/0

involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mutants die within 80 days

tumorigenesis
• adenomas in the small intestine

digestive/alimentary system
• mutants develop an average of 20.1 intestinal polyps per mouse, an 11.17-fold increase over the numbers seen in heterozygous Apc mice


Mouse Genome Informatics
cn86
    Ptentm1Hwu/Ptentm1Hwu
Tg(Vil-cre)997Gum/0

involves: 129S4/SvJae * BALB/c * C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
digestive/alimentary system
• increase in crypt cell proliferation
• intestine is 1.28-fold longer and weighs 1.58-fold more than controls
• however, mutants do not develop polyps
• thickening of the intestinal mucosa
• decrease in the number of enteroendocrine cells
• increase in the number and size of goblet cells
• thickening of the muscular layers of the small intestine
• small intestine exhibits an expanded villus compartment
• mutants exhibit branching of the villi in the small intestine
• small intestine exhibits an expanded crypt compartment with increased number of crypts per villus
• marker analysis indicates impaired Paneth cell maturation
• total protein content of the duodenum is enhanced by 50%
• jejunum exhibits expanded crypt and villus compartments, an increased number of crypts, thickening of the muscular layers and villus branching

endocrine/exocrine glands
• small intestine exhibits an expanded crypt compartment with increased number of crypts per villus
• marker analysis indicates impaired Paneth cell maturation

cellular
• increase in crypt cell proliferation


Mouse Genome Informatics
cn87
    Ptentm1Hwu/Ptentm1Hwu
Tg(Gfap-cre)77.6Mvs/0

involves: 129S4/SvJae * BALB/c * C57BL/6NHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• cultured adult neural stem cells maintain their ability to differentiate into neurons for a longer time compared to wild-type cells
• expansion of the adult neural stem cell and progenitor populations in the subependymal zone
• in culture, neurospheres formed by adult neural stem cells are generally larger and the stem cells' capacity for self renewal is prolonged compared to wild-type cells
• 7 days after induction of limited stroke in the sensorimotor cortex, mice have more neuroblasts in the peri-infarct cortex compared to controls
• however, there is no difference in the number of new cells present at 90 days after stroke induction
• continuous increase in the weight and size of the olfactory bulb compared to controls starting at 2.5 months of age
• the granule cell layer volume is increased 2 fold at 3.5 months of age
• the increase in volume is due to an increase in the number of cells migrating from the subependymal zone to the olfactory bulb and a decrease in the number of apoptotic cells in the granule cell layer
• increase in the volume of the subependymal zone compared to controls
• increase in the number of proliferating cells and DCX positive neuroblasts

behavior/neurological
• habituate faster to a novel odorant compared to controls
• however, no difference in response is seen on the first exposure to a novel odorant

taste/olfaction
• mice recover olfactory ability more quickly following exposure to dichlobenil compared to controls

tumorigenesis
N
• in contrast to other conditional null Pten genotypes no tumors are found in mice up to 2 years of age (J:146630)
(J:154673)

homeostasis/metabolism
• 7 days after induction of limited stroke in the sensorimotor cortex, mice have more neuroblasts in the peri-infarct cortex compared to controls
• however, there is no difference in the number of new cells present at 90 days after stroke induction

cellular
• cultured adult neural stem cells maintain their ability to differentiate into neurons for a longer time compared to wild-type cells
• expansion of the adult neural stem cell and progenitor populations in the subependymal zone
• in culture, neurospheres formed by adult neural stem cells are generally larger and the stem cells' capacity for self renewal is prolonged compared to wild-type cells


Mouse Genome Informatics
cn88
    Krastm4Tyj/Kras+
Ptentm1Hwu/Pten+
Tg(Gfap-cre)77.6Mvs/0

involves: 129S4/SvJae * BALB/c * C57BL/6NHsd
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival is on average 22 weeks

tumorigenesis
• mutants develop multiple visible subcutaneous tumors with 100% penetrance, starting from 4 months of age
• majority of tumors are located on the back and sides
• each mutant has more than one lesion with features of human neurofibroma and malignant peripheral nerve sheath tumor
• progressive development of malignant peripheral nerve sheath tumors (MPNST) from neurofibroma, with 100% of mutants showing MPNST when followed for 7 months
• Pten loss of heterozygosity in mutants correlates with MPNST transformation from neurofibromas

Mouse Models of Human Disease
OMIM IDRef(s)
Neurofibromatosis, Type I; NF1 162200 J:154673


Mouse Genome Informatics
cn89
    Ptentm1Hwu/Ptentm1Hwu
Tg(Nkx2-1-cre)2Sand/0

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• increase in the numbers of Clara cells in the lungs


Mouse Genome Informatics
cn90
    Ptentm1Hwu/Ptentm1Hwu
Slc6a3tm1.1(cre)Bkmn/Slc6a3+

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
N
• no difference in locomotor activity is seen compared to controls during exposure to a novel environment (J:153622)
• mutants exhibit a significant reduction in ipsilateral rotational behavior in response to amphetamine administration after 6OHDA lesioning

nervous system
• neuronal hypertrophy in the ventral midbrain resulting in enlargement of the ventral midbrain area
• increase in the number of TH positive neurons in the substantia nigra compacta and ventral tegmental area of the adult ventral midbrain and an increase in neuronal soma size
• increase in the number of TH positive neurons in the substantia nigra compacta
• increase in the number of dopaminergic neuron dendritic processes in the substantia nigra pars reticulata
• modest but significant enlargement of the caudal striatum
• increase in number of dopaminergic neurons and fibers in the ventral mesencephalon
• dopaminergic neurons in the ventral midbrain are larger in size and have an increase in the number of dendritic processes in the substantia nigra pars reticulata
• hypertrophy of dopamine neurons
• mutant dopamine neurons are protected from 6OHDA induced lesions, fiber loss, and axonal loss in the striatum compared to controls
• increase in total dopamine tissue levels in the dorsal striatum and midbrain, however, no alterations in basal dopamine extracellular levels or evoked dopamine release in the dorsal striatum

homeostasis/metabolism
• increase in total dopamine tissue levels in the dorsal striatum and midbrain, however, no alterations in basal dopamine extracellular levels or evoked dopamine release in the dorsal striatum


Mouse Genome Informatics
cn91
    Ptentm1Hwu/Ptentm1Hwu
Tg(Gdf9-cre)5092Coo/0

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
endocrine/exocrine glands
• females exhibit prematurely activated primordial follicles (transient follicles with enlarged oocytes surrounded by flattened pre-granulosa cells) leading to complete depletion of follicles by 16 weeks of age (J:151696)

reproductive system
• females exhibit prematurely activated primordial follicles (transient follicles with enlarged oocytes surrounded by flattened pre-granulosa cells) leading to complete depletion of follicles by 16 weeks of age (J:151696)


Mouse Genome Informatics
cn92
    Ptentm1Hwu/Ptentm1Hwu
Tg(Scgb1a1-cre)1Tauc/0

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
N
• numbers of bronchioalveolar stem cells in terminal bronchi are normal (J:136369)


Mouse Genome Informatics
cn93
    Krastm4Tyj/Kras+
Ptentm1Hwu/Ptentm1Hwu
Tg(Scgb1a1-cre)1Tauc/0

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
respiratory system
• bronchioles exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls
• mutants exhibit expansion of bronchioalveolar stem cells (BASCs) in terminal bronchi
• small bronchi exhibit clusters of CCSP+SPC+ cells (indicators of BASCs) as early as 4 weeks of age that are not seen in controls


Mouse Genome Informatics
cn94
    Gt(ROSA)26Sortm9(cre/ESR1)Arte/Gt(ROSA)26Sor+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen-treated mice survive 65 days compared with Pdk1tm1Dral Gt(ROSA)26Sortm9(cre/ESR1)Arte mice that survive 57

immune system
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice

tumorigenesis

behavior/neurological
• in tamoxifen-treated mice

hematopoietic system
• in tamoxifen-treated mice
• in tamoxifen-treated mice


Mouse Genome Informatics
cn95
    Gt(ROSA)26Sortm1(H1/tetO-RNAi:Pdpk1)Mrl/Gt(ROSA)26Sortm9(cre/ESR1)Arte
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• tamoxifen-treated mice survive 57 days unlike control mice

immune system
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice

tumorigenesis
• tamoxifen-treated mice develop T cell acute lymphoblastic leukemia unlike control mice

behavior/neurological
• in tamoxifen-treated mice

growth/size
• in tamoxifen-treated mice

integument
• scruffy coat in tamoxifen-treated mice

hematopoietic system
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice
• in tamoxifen-treated mice


Mouse Genome Informatics
cn96
    Amhr2tm3(cre)Bhr/Amhr2+
Ptentm1Hwu/Ptentm1Hwu

involves: 129S4/SvJae * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
N
• no abnormalities in testis (J:187754)
• mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls (J:170203)
• decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front (J:170203)
• 9-fold decrease in apoptotic decidaul cells in mutants relative to controls (J:170203)
• about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma (J:170203)
• these results indicate failure of decidual regression (J:170203)
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc (J:170203)
• endometrium epithelial cells appear hypertrophic, hyperplastic, and disorganized (J:170203)
• about 2-3 days after expected parturition of the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma (J:170203)
• endometrial fibrosis is seen in females beyond the first gestation at day 112.5 and day 119.45 pc (J:170203)
• thickening of the myometrium and disorganization of the muscle fibers before and throughout gestation (J:170203)
• uteri of pregnant females beyond the first gestation, show varying degrees of hyperplasia of both the uterine and glandular epithelia (J:170203)
• primiparous females exhibit reduced fertility due to increased fetal loss at E11.5 (J:170203)
• almost all mutant females fail to carry a second litter to term; females pregnant for the second time show signs of implantation but no viable fetuses at 9.5 dpc (J:170203)
• females produce about 44% fewer pups per mating than controls
• implanted fetuses fail to develop to term due to epithelial hyperplasia and other uterine anomalies

embryogenesis
• females at 11.5 days of pregnancy exhibit poorly transformed maternal vasculature in the decidua, showing persistence of the muscular layer of maternal vessels, even deep within the decidual tissue, however maternal vascular transformation appears complete by 14.5 dpc, indicating a transient delay in vasculature transformation (J:170203)
• mean mutant mesometrial maternal decidua surface area is 2.81-fold greater than in controls (J:170203)
• decidua are abnormal in appearance, featuring many mitotic figures in females 11.5 days pregnant, with little evidence of apoptosis, and many cells with unusually abundant cytoplasm, particularly near the trophoblast invasion front (J:170203)
• 9-fold decrease in apoptotic decidaul cells in mutants relative to controls (J:170203)
• about 2-3 days after expected parturition in the second gestation, females show necrotic decidua with transmural pyometritis and edema in the endometrial stroma (J:170203)
• these results indicate failure of decidual regression (J:170203)
• mutant decidua shows 2.63-fold fewer uterine natural killer cells than control females that are 11.5 dpc (J:170203)