Mouse Genome Informatics
cn1
    Ptentm2.1Ppp/Ptentm2.1Ppp
involves: 129S1/Sv
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex exhibit neurons with increased dendritic total length and branch number
• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex exhibit neurons with increased density of dendritic spines
• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex have neurons that exhibit lower input resistance than nearby control neurons without adenovirus
• pyramidal neurons from mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex receive stronger local inputs in the auditory cortex than control neurons without adenovirus; the increase is greatest for inputs arising from layer 2 but is present in all layers
• neurons from mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex or the left auditory thalamus exhibit increased neuronal responses to auditory callosal and thalamic inputs as indicated by enhanced light-evoked EPSCs after channelrhodopsin-2 adenoviral expression (which allows for neurons to be excited to fire action potentials by flashing blue light)
• mice injected with an adenovirus expressing Cre recombinase into the left auditory cortex exhibit increased miniature spontaneous EPSC frequency and miniature EPSC amplitude

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:181347


Mouse Genome Informatics
cn2
    Cdkn1btm1Ako/Cdkn1btm1Ako
Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(TPO-cre)1Shk/0

129S1.Cg-Cdkn1btm1Ako Ptentm2.1Ppp Tg(TPO-cre)1Shk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean survival is 21 weeks and all mutants die by 6 months of age

endocrine/exocrine glands

respiratory system
• hyperplastic thyroids cause dyspnea and prevent feeding


Mouse Genome Informatics
cn3
    Cdkn1btm1Ako/Cdkn1b+
Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(TPO-cre)1Shk/0

129S1.Cg-Cdkn1btm1Ako Ptentm2.1Ppp Tg(TPO-cre)1Shk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• mean survival is 58 weeks of age

tumorigenesis
• no gender differences in development of adenomas
• no gender differences in development of carcinomas


Mouse Genome Informatics
cn4
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(TPO-cre)1Shk/0

129S1.Cg-Ptentm2.1Ppp Tg(TPO-cre)1Shk
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• females have a reduced lifespan compared to males, with a mean survival age of 73 weeks compared to 83 weeks in males
• mutants start to show signs of illness starting after 1 year of age

endocrine/exocrine glands
• enlarged thyroid
• ovariectomization of females results in reduced proliferative index of thyroids to a similar level seen in males

homeostasis/metabolism
• aging mice exhibit suppression of thyroid-stimulating hormone
• thyroxine levels are slightly, but significantly, increased in all mice with adenomas

tumorigenesis
• 52% of females develop thyroid follicular adenomas between 8-12 months of age compared to 12% of males
• 50% of the females and 35% of males over one year of age develop invasive and often metastatic thyroid follicular carcinomas

Mouse Models of Human Disease
OMIM IDRef(s)
Thyroid Carcinoma, Follicular; FTC 188470 J:165293


Mouse Genome Informatics
cn5
    Pik3cdtm1Tnr/Pik3cdtm1Tnr
Ptentm2.1Ppp/Ptentm2.1Ppp
Cd19tm1(cre)Cgn/Cd19+

involves: 129P2/OlaHsd * 129S1/Sv * 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
N
• unlike in Pten deficient mice, B1 B cell numbers are normal in the spleen and peritoneum (J:130950)
• mice exhibit an increase in marginal zone B cells that is not as great as in Pten null mice but more than in wild-type mice
• defects in class switch recombination associated with Pten deficiency are partially reversed

hematopoietic system
• mice exhibit an increase in marginal zone B cells that is not as great as in Pten null mice but more than in wild-type mice
• defects in class switch recombination associated with Pten deficiency are partially reversed


Mouse Genome Informatics
cn6
    Ptentm2.1Ppp/Pten+
Spry1tm1Jdli/Spry1tm1.1Jdli
Spry2tm1Mrt/Spry2tm1.1Mrt
Tg(Osr1-cre)4Mrt/0

involves: 129P2/OlaHsd * 129S1/Sv * 129X1/SvJ * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• evidence of invasion, including clusters of epithelial cells in the mesenchyme and vasculature and loss of the smooth muscle around ducts, is seen associated with high-grade PIN, indicating transition to invasive cancer (J:192348)
• prostates at 6 months of age show multiple, widely spaced areas with low-grade PIN and occasional ducts with high-grade PIN (J:192348)
• at 12-14 months of age, about 50% of ducts show low-grade PIN and about 15% show high-grade PIN compared to 5-10% of control ducts showing PIN (J:192348)
• ductal lumens are filled with atypical and dysplastic cells that distort the overall ductal architecture and are associated with areas of necrosis and abnormal intraepithelial vessels typical of high-grade PIN (J:192348)

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:192348


Mouse Genome Informatics
cn7
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(CAG-Bgeo,-Spry2,-ALPP)1Mrt/0
Tg(Osr1-cre)4Mrt/0

involves: 129P2/OlaHsd * 129S1/Sv * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• PIN is seen in 15% of prostate ducts as early as 2 weeks of age, in 31% of ducts at 4 weeks, and 42% of ducts at 9 months of age (J:192348)


Mouse Genome Informatics
cn8
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tnfrsf4tm2(cre)Nik/Tnfrsf4+

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
immune system
• following immunization
• 3-fold following immunization
• following immunization, mice exhibit an increased in high-affinity antibody titers compared to in similarly treated wild-type mice

hematopoietic system
• following immunization
• 3-fold following immunization
• following immunization, mice exhibit an increased in high-affinity antibody titers compared to in similarly treated wild-type mice


Mouse Genome Informatics
cn9
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(Osr1-cre)4Mrt/0

involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• PIN is seen in 31% of prostate ducts as early as 2 weeks of age, in 66% of ducts at 4 weeks, and 79% of ducts at 9 months of age show extensive high-grade PIN (J:192348)


Mouse Genome Informatics
cn10
    Eif4etm1.1Lfur/Eif4etm1.1Lfur
Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(Pbsn-cre)4Prb/0

involves: 129S1/Sv * 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
• at 7 months, mice exhibit fewer incidence of high grade prostate intraepithelial neoplasia due to delayed onset and decreased cell proliferation compared with Ptentm2.1Ppp/Ptentm2.1Ppp Tg(Pbsn-cre)4Prb mice
• mice do not exhibit infiltrating adenocarcinoma in the prostate unlike Ptentm2.1Ppp/Ptentm2.1Ppp Tg(Pbsn-cre)4Prb mice


Mouse Genome Informatics
cn11
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(Pbsn-cre)8113ANg/0

involves: 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• complete penetrance of invasive and diffuse prostate cancer (J:86212)
• disruption of basement membrane and organ infiltration (J:86212)
• tumors were less diffuse than in homozygotes carrying Tg(Pbsn-cre)4Prb, variably differentiated, and only affected a single lobe (J:86212)

endocrine/exocrine glands
• irregular cells (J:86212)
• focal areas of epithelial hyperplasia (J:86212)
• increased proliferation of epithelial cells (J:86212)
• enlargement of prostate, less pronounced than in homozygotes carrying Tg(Pbsn-cre)4Prb (J:86212)

reproductive system
• irregular cells (J:86212)
• focal areas of epithelial hyperplasia (J:86212)
• increased proliferation of epithelial cells (J:86212)
• enlargement of prostate, less pronounced than in homozygotes carrying Tg(Pbsn-cre)4Prb (J:86212)


Mouse Genome Informatics
cn12
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(GFAP-TAg121)1Tvd/0

involves: 129S1/Sv * C57BL/6 * C57BL/6J * DBA/2 * FVB/N
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice infected with a cre-expression virus exhibit increased angiogenesis in the cerebral cortex compared to in control mice
• mice infected with a cre-expression virus exhibit astrocytmoa with increased invasiveness compared with mice expressing Tg(GFAP-TAg121)1Tvd

tumorigenesis
• mice infected with a cre-expression virus exhibit astrocytmoa with increased invasiveness compared with mice expressing Tg(GFAP-TAg121)1Tvd

cardiovascular system
• mice infected with a cre-expression virus exhibit increased angiogenesis in the cerebral cortex compared to in control mice
• in cerebral cortex injected with cre-expressing virus

cellular
• mice infected with a cre-expression virus exhibit astrocytmoa with increased invasiveness compared with mice expressing Tg(GFAP-TAg121)1Tvd


Mouse Genome Informatics
cn13
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(Pbsn-cre)4Prb/0

involves: 129S1/Sv * C57BL/6 * DBA/2
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
reproductive system
• large, irregular cells, occasionally forming cryptic glandular structures (J:86212)
• prostate epithelial dysplasia (J:86212)
• focal areas of epithelial hyperplasia (J:86212)
• increased proliferation of epithelial cells (J:86212)
• mutant prostates contain a 20-fold increase in senescent epithelial cells compared to wild-type prostates (J:100683)
• massive enlargement of all prostatic lobes evident at 2 to 3 months of age, complete penetrance (J:86212)

tumorigenesis
• tumors were undifferentiated and often affected multiple lobes, suggesting multifocal origns (J:86212)
• complete penetrance of invasive and diffuse prostate cancer with disruption of basement membrane and signs of organ infiltration (J:86212)
• invasive prostatic cancer develops after a 4-6 month latency; however none of the mutants had died of prostatic cancer by 10 months of age (J:100683)
• tumors retain clearly defined urogenital organ boundaries (J:100683)
• high-grade prostatic intraepithelial neoplasia are seen in all 3 prostatic lobes in 9-week old mutants (J:100683)
(J:163589)
• that does not progress to grossly invasive disease (J:200002)

endocrine/exocrine glands
• large, irregular cells, occasionally forming cryptic glandular structures (J:86212)
• prostate epithelial dysplasia (J:86212)
• focal areas of epithelial hyperplasia (J:86212)
• increased proliferation of epithelial cells (J:86212)
• mutant prostates contain a 20-fold increase in senescent epithelial cells compared to wild-type prostates (J:100683)
• massive enlargement of all prostatic lobes evident at 2 to 3 months of age, complete penetrance (J:86212)


Mouse Genome Informatics
cn14
    Ptentm2.1Ppp/Ptentm2.1Ppp
Trp53tm1Thl/Trp53tm1Thl
Tg(Pbsn-cre)4Prb/0

involves: 129S1/Sv * 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
• all mutants died by 7 months of age

tumorigenesis
• by 11 weeks of age invasive adenocarcinoma develops
• invasive prostatic cancer is seen in all mutants by 10 weeks of age (J:100683)
• average tumor weight is increased 32-fold compared to mutants wild-type for Trp53 and these tumors encompass the entire genitourinary tract and pelvis (J:100683)
• no increase is seen in the number of senescent cells compared to wild-type prostates unlike in mutants wild-type for Trp53 (J:100683)

renal/urinary system
• bladder obstruction


Mouse Genome Informatics
cn15
    Gt(ROSA)26Sortm1(TMPRSS2/ERG)Key/Gt(ROSA)26Sortm1(TMPRSS2/ERG)Key
Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(Pbsn-cre)4Prb/0

involves: 129S1/Sv * 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
• shortened survival compared with Ptentm2.1Ppp/Ptentm2.1Ppp Tg(Pbsn-cre)4Prb mice (J:200002)

reproductive system
• enlarged and hardened by 6 months (J:200002)
• proliferative index only slightly higher than in Ptentm2.1Ppp/Ptentm2.1Ppp Tg(Pbsn-cre)4Prb mice (J:200002)
(J:200002)

tumorigenesis
• invasive with small irregular glandular structures composed of malignant cells with large, pleiomorphic nuclei and pale cytoplasm by 8 weeks (J:200002)
• with a proliferative index only slightly higher than in Ptentm2.1Ppp/Ptentm2.1Ppp Tg(Pbsn-cre)4Prb mice (J:200002)

renal/urinary system
(J:200002)

growth/size
• increased abdominal girth (J:200002)

endocrine/exocrine glands
• enlarged and hardened by 6 months (J:200002)
• proliferative index only slightly higher than in Ptentm2.1Ppp/Ptentm2.1Ppp Tg(Pbsn-cre)4Prb mice (J:200002)


Mouse Genome Informatics
cn16
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(Cnp-EGFR)10Nrat/0
Tg(Dhh-cre)1Mejr/0

involves: 129S1/Sv * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• rapid postnatal death, with a medial survival age of 26 days

nervous system
• mutants exhibit enlarged peripheral nerves: brachial plexi, sacral plexi, trigeminal and sciatic nerves
• 100% exhibit enlarged branchial plexi
• 50% exhibit enlarged lumbar sacral plexi
• mast cells are seen in enlarged peripheral nerves
• 92% exhibit enlarged trigeminal nerves
• mutants exhibit multiple enlarged dorsal root ganglia
• 50% exhibit enlarged sciatic nerves

tumorigenesis
• enlarged peripheral nerves are graded as high-grade grade peripheral nerve sheath tumors (PNSTs) resembling human sporatic malignant grade peripheral nerve sheath tumors


Mouse Genome Informatics
cn17
    Ptentm2.1Ppp/Pten+
Tg(Cnp-EGFR)10Nrat/0
Tg(Dhh-cre)1Mejr/0

involves: 129S1/Sv * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
nervous system
• mice display a similar peripheral nervous system phenotype as homozygous Ptentm2.1Ppp Tg(Dhh-cre)1Mejr/0 mice, except with a latency of 415 days
• 100% exhibit enlarged branchial plexi
• 20% exhibit enlarged sacral plexi
• 100% exhibit enlarged trigeminal nerves
• 80% exhibit enlarged sciatic nerves

tumorigenesis
• enlarged peripheral nerves are graded as hyperplasia to low-grade grade peripheral nerve sheath tumors (PNSTs)


Mouse Genome Informatics
cn18
    Ptentm2.1Ppp/Ptentm2.1Ppp
Tg(Dhh-cre)1Mejr/0

involves: 129S1/Sv * C57BL/6 * FVB/N * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• median survival age is 247 days compared to conditional Pten heterozygotes that have a median survival age of 415 days

nervous system
• mutants exhibit a similar peripheral nervous system phenotype as triple homozygous Ptentm2.1Ppp Tg(Dhh-cre)1Mejr/0 Tg(Cnp-EGFR)10Nrat/0 mutants but with delayed latency and reduced tumor multiplicity
• 100% exhibit enlarged branchial plexi
• 10% exhibit enlarged sacral plexi
• 90% exhibit enlarged trigeminal nerves
• 80% exhibit enlarged sciatic nerves

tumorigenesis
• enlarged peripheral nerves are low-grade peripheral nerve sheath tumors (PNSTs)