Mouse Genome Informatics
hm1
    Ptentm1Rps/Ptentm1Rps
involves: 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• lethality occurs after implantation but prior to gestation, between E6.5 and E9.5
• at E6.5, abnormal embryos appear to undergo a process of resorption

embryogenesis
• embryos appear disorganized at E6.5


Mouse Genome Informatics
ht2
    Ptentm1Rps/Pten+
B6.129S1-Ptentm1Rps
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 12 week old females do not show preference for spending more time in the social chamber versus nonsocial chamber as wild-type mice do and spend equal time in both chambers, indicating impaired social approach behavior in females but not males
• while 8 week old males do not show a change in preference for social interaction for the first trial, upon reexposure to the same social target in trial 2, males do not show attenuation of preference for social investigation between the first and second trials as seen in wild-type mice

nervous system
• both males and females show deficits in prepulse inhibition of the acoustic startle response
• however, mice respond to the olfactory-habituation-dishabituation test normally, indicating normal olfactory function

growth/size
• macrocephaly in both males and females


Mouse Genome Informatics
ht3
    Ptentm1Rps/Pten+
involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 10% of prostates and by 12 months of age, 34% of prostates are still lesion-free (J:75085)
• lesions show absence of Nkx3-1 protein expression (J:75085)

reproductive system
• prostates exhibit localized regions of severely dysplastic epithelium at 6 months of age (J:75085)

endocrine/exocrine glands
• prostates exhibit localized regions of severely dysplastic epithelium at 6 months of age (J:75085)


Mouse Genome Informatics
ht4
    Ptentm1Rps/Pten+
involves: 129S1/Sv * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Gut polyps and lymphoid hyperplasia in Ptentm1Rps/Pten+ mice

mortality/aging
• about 12% of older mice ranging in age from 20-56 weeks die or were sacrificed due to morbidity

tumorigenesis
• neoplasms in multiple organs including the endometrium, liver, prostate, gastrointestinal tract, thyroid, and thymus
• tumors of the gastrointestinal epithelium develop in association with gut lymphoid tissue
• tumors of the endometrium, thyroid, prostate, and liver are not associated with lymphoid tissue and appear highly mitotic
• the tumors that cause morbidity include lymphomas, synchronous thyroid carcinoma, liver adenoma, poorly differentiated leukemia and teratoma
• poorly differentiated leukemia
• lymphomas develop in 7 of 256 mice that were clinically sick
• all mutants that develop lymphoma display diffuse microscopic infiltration of all organs by atypical immature lymphoid cells
• 3 of 8 males at 6-22 weeks of age display prostatic intraepithelial neoplasia; an additional 3 mice have foci of benign epithelial hyperplasia in the prostate (J:53065)

digestive/alimentary system
• intestinal polyps are seen in all mutants from 7 to 18 weeks of age; multiple polyps frequently cluster within a single region
• most polyps are lymphoid polyps with normal epithelium; the second most frequent type of polyp is lymphoid polyps with epithelial hyperplasia

endocrine/exocrine glands
• 5 of the 7 mutants that develop lymphoma have an enlarged thymus
• 3 of 20 mutants at 6-22 weeks of age display follicular or papillary noninvasive neoplasia of the thyroid and an additional 3 mice have atypical epithelial changes in the thyroid

hematopoietic system
• 5 of the 7 mutants that develop lymphoma have an enlarged thymus
• all mutants that develop lymphoma have splenomegaly
• by 50 weeks of age, all females and 45% of males have splenomegaly

immune system
• 5 of the 7 mutants that develop lymphoma have an enlarged thymus
• all mutants that develop lymphoma have splenomegaly
• by 50 weeks of age, all females and 45% of males have splenomegaly
• in the hyperplastic lymph nodes and aggregates, follicular organization is blurred with mixing of the B and T cell regions
• neoplastic hyperplasia of lymph nodes caused by a defect in apoptosis in B cells and macrophages
• expansion of the interfollicular areas, medullary cords, and residual follicular and paracortical hyperplasia composed of B, T, macrophage, and fibroblast cells

reproductive system
• 100% of females aged 18-39 weeks display multifocal endometrial complex atypical hyperplasia, a lesion that is a precursor of endometrial carcinoma (J:53065)


Mouse Genome Informatics
cn5
    Cdkn2atm1Rdp/Cdkn2atm1Rdp
Ptentm1Rps/Ptentm1Rps
Tg(Tyr-cre/ERT2)13Bos/0

involves: 129/Sv * 129S1/Sv * C57BL/6J * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following 4-hydroxytamoxifen (4-OHT) application, all mice develop melanoma over a 9 month period unlike wild-type mice


Mouse Genome Informatics
cn6
    Cdkn2atm1Rdp/Cdkn2atm1Rdp
Ctnnb1tm1Mmt/Ctnnb1tm1Mmt
Ptentm1Rps/Ptentm1Rps
Tg(Tyr-cre/ERT2)13Bos/0

involves: 129/Sv * C57BL/6J * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• following 4-hydroxytamoxifen (4-OHT) application, all mice develop melanoma over a 9 month period unlike wild-type mice


Mouse Genome Informatics
cx7
    Ptentm1Rps/Pten+
Slc6a4tm1Kpl/Slc6a4+

B6.129-Slc6a4tm1Kpl Ptentm1Rps
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• 8 week old females show a significant decrease in preference for interacting with a stimulus mouse in a social approach assay, with mice spending significantly less time interacting with the stimulus mouse than in wild-type mice or either single heterozygote, indicating impaired social approach behavior in females
• while 8 week old males do not show a change in preference for social interaction for the first trial, upon reexposure to the same social target in trial 2, males do not show attenuation of preference for social investigation between the first and second trials as seen in wild-type mice, indicating impaired social recognition in males

nervous system
• deficits in prepulse inhibition of the acoustic startle response indicate impaired sensorimotor gating
• mice show deficits in prepulse inhibition of the acoustic startle response to a similar level as single Pten heterozygotes
• however, mice respond to the olfactory-habituation-dishabituation test normally, indicating normal olfactory function

growth/size
• macrocephaly that is more severe than in either single heterozygote

Mouse Models of Human Disease
OMIM IDRef(s)
Autism 209850 J:144937


Mouse Genome Informatics
cx8
    Ptentm1Rps/Pten+
RictorGt(RRR347)Byg/Rictor+

involves: 129P2/OlaHsd * 129S1/Sv * 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
• double mutants tend to live longer than single heterozygous Pten mice

endocrine/exocrine glands
• prostates exhibit signs of hyperplasia but lesions are less severe than in single heterozygous Pten mice (J:144810)

reproductive system
• prostates exhibit signs of hyperplasia but lesions are less severe than in single heterozygous Pten mice (J:144810)

tumorigenesis
• mutants are protected from prostate cancer development: only 1 of 10 double mutants developed a tumor compared to 5 of 9 single heterozygous Pten mice


Mouse Genome Informatics
cx9
    Ptentm1Rps/Pten+
Rptortm1Lex/Rptor+

involves: 129S/SvEvBrd * 129S1/Sv * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• mutants exhibit a similar lifespan as single heterozygous Pten mice (J:144810)


Mouse Genome Informatics
cx10
    Nkx3-1tm1Mms/Nkx3-1tm1Mms
Ptentm1Rps/Pten+

involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• early carcinoma lesions are seen in the prostate at 6 months of age (J:75085)
• at 6 months of age, high-grade prostatic intraepithelial neoplasia /early carcinoma lesions are seen in 60% of prostates and by 10 months of age, all mice show lesions (J:75085)
• multifocal lesions are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures (J:75085)
• lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index (J:75085)
• lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten (J:75085)

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:75085


Mouse Genome Informatics
cx11
    Nkx3-1tm1Mms/Nkx3-1+
Ptentm1Rps/Pten+

involves: 129S1/Sv * 129S1/SvImJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• early carcinoma lesions are seen in the prostate at 6 months of age (J:75085)
• at 6 months of age, high-grade prostatic intraepithelial neoplasia/early carcinoma lesions are seen in 36% of prostates, and by 12 months, all mice show lesions (J:75085)
• multifocal lesions in the prostate are comprised of poorly differentiated cells with prominent and multiple nucleoli, an increased nuclear/cytoplasmic ratio, and frequent mitotic figures (J:75085)
• lesions usually fill the affected prostatic ducts and are highly vascularized, show an increase in cytokeratins, an absence of basal epithelium, and a high proliferative index (J:75085)
• lesions show absence of Nkx3-1 protein expression, although mRNA is present and allelic loss of Pten (J:75085)

Mouse Models of Human Disease
OMIM IDRef(s)
Prostate Cancer 176807 J:75085


Mouse Genome Informatics
cx12
    MtorGt(OST92090)Lex/Mtor+
Ptentm1Rps/Pten+

involves: 129S1/Sv * 129S5/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• double mutants live longer than single heterozygous Pten mice


Mouse Genome Informatics
cx13
    Mlst8tm1Lex/Mlst8+
Ptentm1Rps/Pten+

involves: 129S1/Sv * 129S5/SvEvBrd * C57BL/6
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• double mutants live longer than single heterozygous Pten mice


Mouse Genome Informatics
cx14
    Ptentm1Rps/Pten+
Tg(Wnt1)1Hev/0

involves: 129S1/Sv * C57BL/6 * FVB * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
tumorigenesis
• mutants occasionally show pulmonary metastasis
• tumors are adenocarcinomas with cribiform, cystic and focal papillary growth patterns
• 50% of males develop tumors by 5.5 months and all males develop tumors within 10 months
• 50% of females develop tumors by 3.5 months of age and all females have tumors within 5 months of age
• 6 of 22 tumors in males are bilateral or unilateral muzzle tumors of epithelial origin
• 7 or 11 tumors show loss of Pten heterozygosity
• most mutants (38 of 49) develop only one palpable tumor
• 14 of 22 tumors in males arise in the salivary tissue (J:67497)
• 50% of females develop mammary ductal carcinoma by 3.5 months of age, earlier than single Tg(Wnt1)1Hev hemizygotes, and all females show tumors by 5 months of age
• 2 of 22 tumors in males are mammary in origin

Mouse Models of Human Disease
OMIM IDRef(s)
Breast Cancer 114480 J:67497