Phenotypes Associated with This Genotype

Genotype
MGI:6715101

• Allelic Composition: Fdxr^tm1Xch/Fdxr⁺
• Genetic Background: B6.Cg-Fdxr^tm1Xch

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

mortality/aging

premature death ( J:244082 , J:360976 )

• although heterozygotes appear healthy with no obvious abnormalities during the first 6 months of life, median survival is significantly shorter than that for wild-type controls (102 weeks versus 117 weeks) (J:244082)

neoplasm

increased tumor incidence ( J:244082 , J:360976 )

• heterozygotes are prone to a wide spectrum of spontaneous tumors; 89.7% of mice develop tumors versus 22.2% of wild-type controls (J:244082)

• 26 of 29 mice develop spontaneous tumors relative to 11 of 51 wild-type controls (J:360976)

increased liver tumor incidence ( J:244082 )

• 11 of 29 mice develop liver tumors

• liver tumor tissue shows increased transcript levels of alpha-fetoprotein (a hepatocellular carcinoma biomarker) as well as decreased reticulin staining along with widened trabeculae, encompassing 3 or more cell layers

• however, RT-PCR analysis revealed no mutation in the p53 DNA-binding domain

increased hepatocellular carcinoma incidence ( J:244082 )

• 2 of 11 liver tumors are hepatocellular carcinomas (HCCs)

increased hemangioma incidence ( J:244082 )

• 3 of 29 mice develop hemangiomas

increased lymphoma incidence ( J:244082 )

• 19 of 29 mice develop high-grade lymphomas

increased T cell derived lymphoma incidence ( J:244082 )

• 5 of 29 mice develop T-cell lymphomas

increased B cell derived lymphoma incidence ( J:244082 )

• 12 of 29 mice develop B-cell lymphomas

increased lung carcinoma incidence ( J:244082 )

• 4 of 29 mice develop lung carcinomas

increased sarcoma incidence ( J:244082 )

• 7 of 29 mice develop high-grade malignant sarcomas

increased hemangiosarcoma incidence ( J:244082 )

• 3 of 29 mice develop angiosarcomas

increased myeloid sarcoma incidence ( J:244082 )

• 2 of 29 mice develop myeloid sarcomas

increased plasmacytoma incidence ( J:244082 )

• 1 of 29 mice develop plasmacytomas

homeostasis/metabolism

abnormal iron homeostasis ( J:244082 )

• liver tissues and mouse embryonic fibroblasts (MEFs) show increased protein expression of IREB2 (iron responsive element binding protein 2; aka IRP2) and TFRC (transferrin receptor; aka TfR1) but reduced expression of ACO1 (aconitase 1; aka IRP1) and FTH1 (ferritin heavy polypeptide 1)

abnormal iron level ( J:244082 )

• Pearl's Prussian blue staining revealed moderate iron accumulation in E8.0 embryos

• a QuantiChrom iron assay showed an increased iron level in the mitochondria but not in the cytoplasm of heterozygous MEFs

increased liver iron level ( J:244082 )

• Pearl's Prussian blue staining revealed extensive iron accumulation in hepatocytes

abnormal protein level ( J:244082 )

• liver tissues and MEFs show reduced protein levels of tumor protein p53 and CDKN1A (aka p21)

• however, RT-PCR showed that Trp53 mRNA levels in MEFs are normal

increased alpha-fetoprotein level ( J:244082 )

• liver tumor tissue shows increased transcript levels of alpha-fetoprotein (a hepatocellular carcinoma biomarker)

liver/biliary system

increased liver iron level ( J:244082 )

• Pearl's Prussian blue staining revealed extensive iron accumulation in hepatocytes

chronic liver inflammation ( J:244082 )

• 10 of 29 mice exhibit chronic hepatitis

hepatic steatosis ( J:244082 )

• 15 of 29 mice exhibit liver steatosis

increased liver tumor incidence ( J:244082 )

• 11 of 29 mice develop liver tumors

• liver tumor tissue shows increased transcript levels of alpha-fetoprotein (a hepatocellular carcinoma biomarker) as well as decreased reticulin staining along with widened trabeculae, encompassing 3 or more cell layers

• however, RT-PCR analysis revealed no mutation in the p53 DNA-binding domain

increased hepatocellular carcinoma incidence ( J:244082 )

• 2 of 11 liver tumors are hepatocellular carcinomas (HCCs)

cellular

abnormal mitochondrial morphology ( J:244082 )

• MEFs show mitochondrial iron accumulation

decreased cell death ( J:244082 )

• RSL3- and erastin-induced ferroptosis is inhibited in MEFs

increased fibroblast proliferation ( J:244082 )

• MEFs show increased proliferation over a 6-d period

immune system

increased T cell derived lymphoma incidence ( J:244082 )

• 5 of 29 mice develop T-cell lymphomas

chronic liver inflammation ( J:244082 )

• 10 of 29 mice exhibit chronic hepatitis

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:244082 )

• 5 of 29 mice develop T-cell lymphomas

respiratory system

increased lung carcinoma incidence ( J:244082 )

• 4 of 29 mice develop lung carcinomas

hematopoietic system

increased T cell derived lymphoma incidence ( J:244082 )

• 5 of 29 mice develop T-cell lymphomas