Phenotypes Associated with This Genotype

Genotype
MGI:2682002

• Allelic Composition: Nbn^tm1Zqw/Nbn⁺
• Genetic Background: involves: 129S2/SvPas * C57BL/6

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

mortality/aging

increased mortality induced by gamma-irradiation ( J:86563 )

• heterozygotes irradiated with gamma-rays at a dosage of 8 Gy exhibit a significantly shorter life span than wild-type controls

neoplasm

increased tumor incidence ( J:86563 )

• over a period of 100 weeks, heterozygotes exhibit increased susceptibility to spontaneous tumor development (78% vs 53% in wild-type), with a significantly higher number of tumors per mouse than wild-type mice (1.09 vs 0.59, respectively)

• heterozygotes develop a high frequency of epithelial tumors (52%), gonad tumors (12%), and lymphomas (10%), whereas wild-type mice develop primarily age-related tumors such as lung tumors, angiomas, and sarcomas

increased thyroid adenoma incidence ( J:86563 )

• heterozygotes develop a high frequency of thyroid gland atypical hyperplasia and intraepithelial adenomas only after gamma-irradiation

increased mammary adenocarcinoma incidence ( J:86563 )

• ~3.5% of heterozygotes develop mammary gland adenocarcinomas vs none of wild-type mice

increased prostate intraepithelial neoplasia incidence ( J:86563 )

♂ • 8.6% of heterozygotes develop low-grade prostate intraepithelial neoplasia vs none of wild-type mice

increased liver adenocarcinoma incidence ( J:86563 )

• 8.6% of heterozygotes develop liver adenocarcinomas vs 3% of wild-type mice

increased liver adenoma incidence ( J:86563 )

• 10% of heterozygotes develop liver adenomas vs 6.5% of wild-type mice

increased lymphoma incidence ( J:86563 )

• 10% of heterozygotes develop lymphomas that can infiltrate other organs such as the liver or small intestine and express exclusively either the B-cell marker CD45R/B220, or the T-cell marker CD3

increased T cell derived lymphoma incidence ( J:86563 )

increased B cell derived lymphoma incidence ( J:86563 )

increased lung adenocarcinoma incidence ( J:86563 )

• heterozygotes exhibit an increased frequency of lung adenocarcinomas after gamma-irradiation

increased incidence of tumors by ionizing radiation induction ( J:86563 )

• tumor incidence is dramatically increased in gamma-irradiated heterozygotes (85% vs 41% in wild-type control mice), with more lymphomas and epithelial tumors detected in radiation-treated heterozygotes relative to wild-type controls or to unirradiated groups

• more lymphomas and epithelial tumors are observed in radiation-treated heterozygotes relative to wild-type controls or to unirradiated groups

• gamma-irradiation induces a high frequency of thyroid gland atypical hyperplasia and intraepithelial adenomas, and enhances the formation of lung cancers, germ cell tumors and stromal cell tumors in the testis (Leydig cell tumors) and ovary

increased gonad tumor incidence ( J:86563 )

• 12% of heterozygotes develop gonad tumors, including sex-cord stromal cell tumors (7%) and germ cell tumors (5%)

• heterozygotes exhibit an increased frequency of germ cell tumors and stromal cell tumors in the testis (Leydig cell tumors) and ovary after gamma-irradiation

increased Leydig cell tumor incidence ( J:86563 )

♂ • heterozygotes exhibit an increased frequency of Leydig cell tumors after gamma-irradiation

decreased tumor latency ( J:86563 )

• heterozygotes exhibit an earlier tumor onset

cellular

chromosomal instability ( J:86563 )

• MEFs and tumor cellss derived from heterozygous mutant mice show an increased rate of chromosome aberrations, including chromosome end-to-end fusions and fragmentations, as well as loss of telomeres at the fusion sites

homeostasis/metabolism

increased mortality induced by gamma-irradiation ( J:86563 )

• heterozygotes irradiated with gamma-rays at a dosage of 8 Gy exhibit a significantly shorter life span than wild-type controls

respiratory system

increased lung adenocarcinoma incidence ( J:86563 )

• heterozygotes exhibit an increased frequency of lung adenocarcinomas after gamma-irradiation

reproductive system

increased prostate intraepithelial neoplasia incidence ( J:86563 )

♂ • 8.6% of heterozygotes develop low-grade prostate intraepithelial neoplasia vs none of wild-type mice

increased gonad tumor incidence ( J:86563 )

• 12% of heterozygotes develop gonad tumors, including sex-cord stromal cell tumors (7%) and germ cell tumors (5%)

• heterozygotes exhibit an increased frequency of germ cell tumors and stromal cell tumors in the testis (Leydig cell tumors) and ovary after gamma-irradiation

increased Leydig cell tumor incidence ( J:86563 )

♂ • heterozygotes exhibit an increased frequency of Leydig cell tumors after gamma-irradiation

liver/biliary system

increased liver adenocarcinoma incidence ( J:86563 )

• 8.6% of heterozygotes develop liver adenocarcinomas vs 3% of wild-type mice

increased liver adenoma incidence ( J:86563 )

• 10% of heterozygotes develop liver adenomas vs 6.5% of wild-type mice

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:86563 )

increased thyroid adenoma incidence ( J:86563 )

• heterozygotes develop a high frequency of thyroid gland atypical hyperplasia and intraepithelial adenomas only after gamma-irradiation

increased mammary adenocarcinoma incidence ( J:86563 )

• ~3.5% of heterozygotes develop mammary gland adenocarcinomas vs none of wild-type mice

increased prostate intraepithelial neoplasia incidence ( J:86563 )

♂ • 8.6% of heterozygotes develop low-grade prostate intraepithelial neoplasia vs none of wild-type mice

increased Leydig cell tumor incidence ( J:86563 )

♂ • heterozygotes exhibit an increased frequency of Leydig cell tumors after gamma-irradiation

integument

increased mammary adenocarcinoma incidence ( J:86563 )

• ~3.5% of heterozygotes develop mammary gland adenocarcinomas vs none of wild-type mice

hematopoietic system

increased T cell derived lymphoma incidence ( J:86563 )

immune system

increased T cell derived lymphoma incidence ( J:86563 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Nijmegen breakage syndrome		DOID:7400	OMIM:251260	J:86563