Phenotypes for Pten Tg(Pbsn-cre)4Prb MGI:4420974 MGI Mouse

mortality/aging

premature death ( J:93902 )

• 3 of 14 mice die by age 12 to 29 weeks

• however, all castrated mice survive from 7 to 10 months

decreased tumor-free survival time ( J:124208 )

• 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

• 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

reproductive system

abnormal prostate gland morphology ( J:124208 )

• prostate lobes are enlarged and exhibit increased vascularity and cellularity

abnormal prostate gland epithelium morphology ( J:93902 )

• at 4 weeks, epithelium cells in the lateral prostate are larger than in Pten^tm1Hwu homozygotes

prostate gland epithelial hyperplasia ( J:93902 )

• without cellular atypia by 4 weeks of age

enlarged prostate gland ( J:93902 )

• mice exhibit progressive enlargement of the prostate gland compared to in Pten^tm1Hwu homozygotes

• however, castration reduces prostate size

increased prostate gland weight ( J:124208 )

• prostate weight is higher than in controls starting at 8 weeks of age

• 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

prostate gland hyperplasia ( J:93902 )

• at 4 weeks, mice develop multifocal hyperplasia compared to in Pten^tm1Hwu homozygotes

• hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes

increased prostate gland tumor incidence ( J:124208 )

• males develop prostate cancer

increased prostate gland adenocarcinoma incidence ( J:93902 , 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)

increased prostate intraepithelial neoplasia incidence ( J:93902 , J:106650 )

• 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)

abnormal prostate gland physiology ( J:93902 , J:124208 )

• prostate cancer cells exhibit increased proliferation compared to in Pten^tm1Hwu homozygotes (J:93902)

• cancer cells induce a desmoplastic response (J:93902)

• castrated mice exhibit increased proliferation compared with similarly treated Pten^tm1Hwu homozygotes (J:93902)

• 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 gland inflammation ( J:93902 )

• cancer cells induce inflammation

neoplasm

increased prostate gland tumor incidence ( J:124208 )

• males develop prostate cancer

increased prostate gland adenocarcinoma incidence ( J:93902 , 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)

increased prostate intraepithelial neoplasia incidence ( J:93902 , J:106650 )

• 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)

decreased tumor incidence ( J:124208 )

• 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

prostate gland inflammation ( J:93902 )

• cancer cells induce inflammation

pyelonephritis ( J:124208 )

• mutants surviving 6 months or longer exhibit pyelonephritis

endocrine/exocrine glands

abnormal prostate gland morphology ( J:124208 )

• prostate lobes are enlarged and exhibit increased vascularity and cellularity

abnormal prostate gland epithelium morphology ( J:93902 )

• at 4 weeks, epithelium cells in the lateral prostate are larger than in Pten^tm1Hwu homozygotes

prostate gland epithelial hyperplasia ( J:93902 )

• without cellular atypia by 4 weeks of age

enlarged prostate gland ( J:93902 )

• mice exhibit progressive enlargement of the prostate gland compared to in Pten^tm1Hwu homozygotes

• however, castration reduces prostate size

increased prostate gland weight ( J:124208 )

• prostate weight is higher than in controls starting at 8 weeks of age

• 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

prostate gland hyperplasia ( J:93902 )

• at 4 weeks, mice develop multifocal hyperplasia compared to in Pten^tm1Hwu homozygotes

• hyperplasia is initially observed in the dorsolateral and ventral lobe with subsequent involvement of the anterior lobes

increased prostate gland tumor incidence ( J:124208 )

• males develop prostate cancer

increased prostate gland adenocarcinoma incidence ( J:93902 , 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)

increased prostate intraepithelial neoplasia incidence ( J:93902 , J:106650 )

• 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)

abnormal prostate gland physiology ( J:93902 , J:124208 )

• prostate cancer cells exhibit increased proliferation compared to in Pten^tm1Hwu homozygotes (J:93902)

• cancer cells induce a desmoplastic response (J:93902)

• castrated mice exhibit increased proliferation compared with similarly treated Pten^tm1Hwu homozygotes (J:93902)

• 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 gland inflammation ( J:93902 )

• cancer cells induce inflammation

renal/urinary system

abnormal renal/urinary system physiology ( J:124208 )

• mutants surviving 6 months or longer exhibit retention of urine in the anterior prostate lobes

pyelonephritis ( J:124208 )

• mutants surviving 6 months or longer exhibit pyelonephritis

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
prostate cancer		DOID:10283	OMIM:176807 OMIM:300147 OMIM:300704 OMIM:601518 OMIM:602759 OMIM:608656 OMIM:608658 OMIM:609299 OMIM:609558 OMIM:610321 OMIM:610997 OMIM:611100 OMIM:611868 OMIM:611928 OMIM:611955 OMIM:611958 OMIM:611959	J:93902

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

Contributing Projects: Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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