Mouse Genome Informatics
cn1
    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
phenotype observed in males
N normal phenotype
tumorigenesis
• mutants develop adenocarcinoma in the dorsolateral lobes of the prostate
• cancer progression is similar to single conditional Pten mice
• proliferation and apoptotic indexes are increased in the cancers, most notably in the proximal regions of the dorsal-lateral lobe
• mutant tumors contain low or no p63+ cells, similar to human prostate cancer
• castrated mutants develop cancer outgrowths in the dorsolateral lobes, indicating that mutants develop castrate-resistant prostate cancer
• castrated mice treated with rapamycin show a reduction in prostate volume and reduced prostate proliferation

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


Mouse Genome Informatics
cn2
    Artm1Verh/Y
Plekha5Tg(AMH-cre)1Flor/0

involves: 129S1/Sv * 129X1/SvJ * Black Swiss * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• at P50, reduced male germ cell numbers were associated with a 4-5-fold increase in germ cell apoptosis
• as expected, Leydig cell cytoplasmic volume was relatively constant up to P20 and more than doubled between P20 and P50; however, an additional 32% increase occurred between P50 and P140, such that at P140 cytoplasmic volume was 23% higher than that in controls
• at P50, the volumes of mitochondria and lipid droplets were 2-fold higher than in controls; however, only the increase in lipid droplets was statistically significant
• although Leydig cell number was normal at P12, it was reduced by >40% at later ages (P20, P50, and P140)
• notably, the temporal pattern of change in LC number was generally similar to that of controls
• at P50 and P140, LC number was significantly higher than in Artm1.1Verh males
• immunohistochemistry and quantitative PCR for LC-specific markers revealed that steroidogenic function per LC was probably increased
• significant reduction in seminiferous tubule diameter at P50
• however, numbers of Sertoli cells remained essentially normal based on measurement of nuclear volume per testis
• testes were properly descended but small in size
• normal development of epididymis, vas deferens, coagulating gland, seminal gland, and prostate gland
• normal development of Leydig cells and peritubular myoid cells
• at P50, testis weight was reduced to 28.4% of wild-type weight (J:88169)
• although normal at P12, testis weight was reduced to 53% of control value at P20 and to 25-30% of control value at P50 and P140 (J:100799)
• at P50, numbers of round spermatids were reduced to only 3% of wild-type numbers
• the few round spermatids that formed appeared abnormal and failed to survive beyond stages VII-VIII
• no elongated spermatids were detected
• at P50, numbers of diplotene and secondary spermatocytes were reduced to 64% of wild-type numbers
• reduced germ cell numbers associated with increased apoptosis
• absence of elongated spermatids
• spermatogenic arrest at the late spermatocyte/spermatid stage
• normal entry into meiosis, but progressive loss of pachytene primary spermatocytes between stages VI and XII
• at P50, epididymis weight was reduced by 30% relative to wild-type

homeostasis/metabolism
• at P50, serum FSH leves were elevated by 34% relative to wild-type
• in contrast, serum levels of testosterone and luteinizing hormone remained normal

endocrine/exocrine glands
• as expected, Leydig cell cytoplasmic volume was relatively constant up to P20 and more than doubled between P20 and P50; however, an additional 32% increase occurred between P50 and P140, such that at P140 cytoplasmic volume was 23% higher than that in controls
• at P50, the volumes of mitochondria and lipid droplets were 2-fold higher than in controls; however, only the increase in lipid droplets was statistically significant
• although Leydig cell number was normal at P12, it was reduced by >40% at later ages (P20, P50, and P140)
• notably, the temporal pattern of change in LC number was generally similar to that of controls
• at P50 and P140, LC number was significantly higher than in Artm1.1Verh males
• immunohistochemistry and quantitative PCR for LC-specific markers revealed that steroidogenic function per LC was probably increased
• significant reduction in seminiferous tubule diameter at P50
• however, numbers of Sertoli cells remained essentially normal based on measurement of nuclear volume per testis
• testes were properly descended but small in size
• normal development of epididymis, vas deferens, coagulating gland, seminal gland, and prostate gland
• normal development of Leydig cells and peritubular myoid cells
• at P50, testis weight was reduced to 28.4% of wild-type weight (J:88169)
• although normal at P12, testis weight was reduced to 53% of control value at P20 and to 25-30% of control value at P50 and P140 (J:100799)

growth/size/body
N
• growth curves of hemizygous mutant males were similar to those of wild-type males

cellular
• at P50, reduced male germ cell numbers were associated with a 4-5-fold increase in germ cell apoptosis


Mouse Genome Informatics
cn3
    Artm1Verh/Y
Tg(Fabp4-cre)1Rev/0

involves: 129S1/Sv * 129X1/SvJ * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
adipose tissue
• while males on a normal chow diet are not obese, they show reduced perigonadal fat weight but increased interscapular brown adipose tissue at 3 months age
• however, body fat composition is no longer different by 6 months of age
• on a high-fat diet, males gain equal weight compared with controls, however after 24 weeks, they have more visceral fat, with increases in omental and mesenteric fat pad weights
• on a normal chow diet, males have an increase in interscapular brown adipose tissue at 3 months of age
• however, white adipose tissue morphology in the perigonadal and subcutaneous depots are normal
• on a normal chow diet, males have reduced perigonadal fat weight and proportion
• after 24 weeks of a high-fat diet, males show an increase in mesenteric fat pad weight compared to controls
• after 24 weeks of a high-fat diet, males show an increase in omental fat pad weight compared to controls
• on a normal chow diet, males have an increase in interscapular brown adipose tissue at 3 months of age

growth/size/body
• on a normal chow diet, males gain less weight than controls at 3 months of age

homeostasis/metabolism
• males are euglycemic at 3 months of age, however between 3 and 12 months of age, males are unable to sustain the normal increase in insulin secretory capacity, and they develop hyperglycemia
• after 24 weeks on a high-fat diet, mutants have a poorer secretory response and become more hyperglycemic than controls
• males are euglycemic but hyperinsulinemic both in the fasted state and during glucose tolerance testing at 3 months of age
• 3 month old males have elevated plasma triglyceride levels but normal liver triglycerides
• males show age-related glucose intolerance
• insulin resistance in 3 month old males on a normal diet, as indicated by hyperinsulinemia both in the fasted state and during glucose tolerance

Mouse Models of Human Disease
OMIM IDRef(s)
Diabetes Mellitus, Noninsulin-Dependent; NIDDM 125853 J:196857


Mouse Genome Informatics
cn4
    Artm1Verh/Y
Rnase10tm1(cre)Hht/Rnase10+

involves: 129S7/SvEvBrd * C57BL/6
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
• undergoing degeneration at 4 months
• germinal epithelium lost in many tubules
• intraepithelial cysts frequently found
• at four months
• as a result of fluid retention
• spermatic granulomata frequently obstruct the epididymes
• initial segment hypoplasia by 30 days
• epididymis becomes obstructed at the level of the caput
• sperm build-up starting around 40 days causes severe dilation and finally, complete occlusion
• decreased height after 20-25 days in segments I and II
• begins to degenerate distal to occlusion
• some males develop unilateral orchitis
• no pregnancies after mating to CD1 females
• vaginal plugs are produced

endocrine/exocrine glands
• intraepithelial cysts frequently found
• undergoing degeneration at 4 months
• germinal epithelium lost in many tubules
• at four months
• as a result of fluid retention
• some males develop unilateral orchitis

immune system
• some males develop unilateral orchitis


Mouse Genome Informatics
ot5
    Artm1Verh/Y
involves: 129S1/Sv * 129X1/SvJ
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
reproductive system
N
• genotypic males had a male phenotype and showed normal development of the male urogenital system