All Phenotypes Clspn<tm1(KOMP)Vlcg> MGI Mouse

reproductive system phenotype ( J:332163 )

N

• at 6 weeks of age, heterozygous females show a slight, non-significant increase in the total number of oocytes, number of immature oocytes, and number of oocytes that fail to arrest in prophase I, with no differences in ovary weight and number of heathy or unhealthy oocytes relative to age-matched wild-type controls

abnormal female meiosis I arrest ( J:332163 )

• oocytes from heterozygous females that fail to extrude the 1st polar body arrest prematurely between mid-late prometaphase I and do not progress to the correct meiosis II (MII) stage

impaired polar body extrusion ( J:332163 )

• in culture, oocytes from heterozygous females cannot efficiently exit meiosis I (MI); the rate of 1st polar body extrusion is significantly lower than that for wild-type oocytes

delayed female fertility ( J:332163 )

• matings involving heterozygous females result in lengthened time to first litter (44.5 days versus 22 days for wild-type mice)

abnormal pregnancy ( J:332163 )

• heterozygous matings result in a high first pregnancy failure rate with signs of pregnancy re-absorption at E17.5

• however, this improves over time and heterozygous females go on to have full-term pregnancies and produce healthy offspring born at expected Mendelian ratios

reduced female fertility ( J:332163 )

• matings involving heterozygous females result in significantly fewer litters (2.2 versus 5 for wild-type mice in 100 days)

decreased litter size ( J:332163 )

• matings involving heterozygous females result in a decreased average number of pups per litter (3.8 versus 7.2 for wild-type mice)

increased B cell number ( J:332163 )

• mesenteric lymph nodes exhibiting hyperplasia show increased staining for the lymphocyte marker CD45R

lymphoid hyperplasia ( J:332163 )

• aged heterozygotes develop spontaneous B-cell lymphoid hyperplasia: at 18 months of age, 5 of 9 heterozygotes born to wild-type mothers exhibit hyperplasia of the mesenteric lymph nodes while 2 of 9 show additional hyperplasia in other lymph nodes

• although mesenteric lymph nodes appear larger, no significant changes are detected in the weight of mesenteric or other lymph nodes with hyperplasia at any time points

increased bone marrow cell number ( J:332163 )

• aged heterozygotes that exhibit mesenteric lymph node hyperplasia also show increased bone marrow cellularity

increased B cell number ( J:332163 )

• mesenteric lymph nodes exhibiting hyperplasia show increased staining for the lymphocyte marker CD45R

increased susceptibility to weight gain ( J:332163 )

• at 12 months of age, male, but not female, heterozygotes gain weight more rapidly than wild-type controls

increased liver weight ( J:332163 )

• at 12 months of age, male heterozygotes exhibit heavier livers and a higher liver to body weight ratio than aged-matched wild-type controls

abnormal embryo development ( J:332163 )

• heterozygous matings result in heterozygous embryos with marked developmental defects at E13.5, ranging from undersized embryos to arrest at blastocyst stage

embryonic growth arrest ( J:332163 )

• 5 of 8 heterozygous embryos produced by heterozygous matings arrest at the blastocyst stage

abnormal limb morphology ( J:332163 )

• 2 of 8 heterozygous embryos produced by heterozygous matings show limb deformities

increased hepatocyte proliferation ( J:332163 )

• after partial hepatectomy, 12-week-old male heterozygotes show higher liver:body weight ratios than wild-type controls, suggesting a greater rate of hepatocyte proliferation following acute liver injury

increased liver weight ( J:332163 )

• at 12 months of age, male heterozygotes exhibit heavier livers and a higher liver to body weight ratio than aged-matched wild-type controls

increased susceptibility to age-related hepatic steatosis ( J:332163 )

• at 12 months of age, the livers of 4 of 5 heterozygotes show macroscopic signs of damage with large, widespread fat droplets and inflammatory infiltrates indicative of both micro- and macro-steatohepatitis

increased susceptibility to diet-induced hepatic steatosis ( J:332163 )

• after short periods on a methionine and choline deficient (MCD) diet, male heterozygotes show a significant decrease in the liver:body weight ratio and higher lobular inflammation counts than wild-type controls, indicating increased susceptibility to non-alcoholic fatty liver disease

enhanced liver regeneration ( J:332163 )

• after partial hepatectomy, 12-week-old male heterozygotes show higher liver:body weight ratios than wild-type controls, indicating increased liver regeneration

abnormal intestine morphology ( J:332163 )

• 2 of 9 aged heterozygotes born to wild-type mothers show hyperplasia of the small intestine/colon in addition to mesenteric lymph node hyperplasia

increased incidence of tumors by chemical induction ( J:332163 )

• at 30 weeks after DEN administration to 15-day-old mice, heterozygotes exhibit significantly higher numbers of mitotic bodies in tumors and more malignant hepatocellular carcinoma (HCC) numbers than wild-type controls: 13 heterozygotes had 23 HCCs in total, including one mouse with 2 grade II and one mouse with 1 grade III HCC versus only six grade I HCCs in wild-type controls

decreased tumor latency ( J:332163 )

• at 30 weeks after DEN administration to 15-day-old mice, heterozygotes show a significantly higher liver-to-body weight ratio than wild-type controls, suggesting an earlier onset of tumorigenesis in the chronic model of DEN-induced hepatocellular carcinomas

abnormal DNA repair ( J:332163 )

• after acute N-nitrosodiethylamine (DEN) treatment, liver DNA damage (measured by gammaH2AX staining) persists for a longer period than in DEN-treated wild-type controls, suggesting that DNA mutations remain unrepaired during subsequent compensatory proliferation

increased incidence of tumors by chemical induction ( J:332163 )

• at 30 weeks after DEN administration to 15-day-old mice, heterozygotes exhibit significantly higher numbers of mitotic bodies in tumors and more malignant hepatocellular carcinoma (HCC) numbers than wild-type controls: 13 heterozygotes had 23 HCCs in total, including one mouse with 2 grade II and one mouse with 1 grade III HCC versus only six grade I HCCs in wild-type controls

increased susceptibility to injury ( J:332163 )

• after partial hepatectomy, 12-week-old male heterozygotes show a significantly higher % of gammaH2AX+ pixels indicative of DNA damage than wild-type controls, indicating increased susceptibility to acute liver injury

• after acute N-nitrosodiethylamine (DEN) treatment, 8-week-old male heterozygotes show a significantly lower body weight and liver-to-body weight ratio and more pronounced DNA damage that persists for a longer period of time than in DEN-treated wild-type controls