Phenotypes associated with this allele

• Allele Symbol: Nbn^em7Jpt
• Allele Name: endonuclease-mediated mutation 7, John H Petrini
• Allele ID: MGI:6771585
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Nbn^em7Jpt/Nbn^em7Jpt	Not Specified	MGI:6780000
cn2	Nbn^em7Jpt/Nbn^tm2Zqw Tg(VAV1-cre)1Graf/0	involves: 129P2/OlaHsd	MGI:6771693

Genotype
MGI:6780000

hm1

• Allelic Composition: Nbn^em7Jpt/Nbn^em7Jpt
• Genetic Background: Not Specified

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

mortality/aging

prenatal lethality, complete penetrance ( J:251434 )

• no pups are obtained indicating prenatal lethality

Genotype
MGI:6771693

cn2

• Allelic Composition: Nbn^em7Jpt/Nbn^tm2Zqw; Tg(VAV1-cre)1Graf/0
• Genetic Background: involves: 129P2/OlaHsd

mortality/aging

premature death ( J:277750 )

• mice succumb to highly aggressive T cell malignancy with a median lifespan of 169 days

endocrine/exocrine glands

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

increased T cell derived lymphoma incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• lymphomas contain whole chromosome 15 duplications

hematopoietic system

increased pro-B cell number ( J:277750 )

• pro-B cells (CD43+) are increased

impaired hematopoiesis ( J:277750 )

• hematopoiesis is severely impaired

decreased bone marrow cell number ( J:277750 )

• the cellularity of the bone marrow is decreased

thrombocytosis ( J:277750 )

• 2-fold elevation in platelets

decreased leukocyte cell number ( J:277750 )

• white blood cell counts are reduced in 6-to 8-week-old mice

decreased B cell number ( J:277750 )

• the percentage of peripheral B cells is decreased

• percentage of B lineage cells (B220+) is decreased by roughly 3-fold

• depletion of B cell lineage cells coincides with the onset of Ig gene assembly: whereas pro-B cells (CD43+) are increased, the levels of B220+ cell decrease beginning at the pre-B stage when Ig heavy chain rearrangement commences to the immature B cell stage (CD43-)

absent mature B cells ( J:277750 )

• IgM+ mature B cells are virtually undetectable

decreased myeloid cell number ( J:277750 )

• percentage of myeloid cells (Mac-1+ and Gr-1+) is decreased by roughly 3-fold

• however, levels of erythroid precursors (Ter119+) are unchanged

decreased erythrocyte cell number ( J:277750 )

• red blood cell numbers are reduced in 6-to 8-week-old mice

abnormal T cell morphology ( J:277750 )

• an increase in copy number of the MRE11 and CHK1 genes on chromosome 9 is detected in thymocytes as early as 4 weeks of age

• MYC amplification on chromosome 15 is detected in thymocytes at 4 weeks of age

increased CD8-positive, alpha-beta T cell number ( J:277750 )

• CD8+ population is elevated in the thymus at 6 weeks of age

decreased T cell number ( J:277750 )

• the percentage of peripheral T cells is decreased

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

immune system

increased pro-B cell number ( J:277750 )

• pro-B cells (CD43+) are increased

decreased leukocyte cell number ( J:277750 )

• white blood cell counts are reduced in 6-to 8-week-old mice

decreased B cell number ( J:277750 )

• the percentage of peripheral B cells is decreased

• percentage of B lineage cells (B220+) is decreased by roughly 3-fold

• depletion of B cell lineage cells coincides with the onset of Ig gene assembly: whereas pro-B cells (CD43+) are increased, the levels of B220+ cell decrease beginning at the pre-B stage when Ig heavy chain rearrangement commences to the immature B cell stage (CD43-)

absent mature B cells ( J:277750 )

• IgM+ mature B cells are virtually undetectable

abnormal T cell morphology ( J:277750 )

• an increase in copy number of the MRE11 and CHK1 genes on chromosome 9 is detected in thymocytes as early as 4 weeks of age

• MYC amplification on chromosome 15 is detected in thymocytes at 4 weeks of age

increased CD8-positive, alpha-beta T cell number ( J:277750 )

• CD8+ population is elevated in the thymus at 6 weeks of age

decreased T cell number ( J:277750 )

• the percentage of peripheral T cells is decreased

decreased thymocyte number ( J:277750 )

• the cellularity of the thymus is decreased, with decreased thymocyte numbers

neoplasm

increased T cell derived lymphoma incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• lymphomas contain whole chromosome 15 duplications

increased T cell acute lymphoblastic leukemia incidence ( J:277750 )

• 90% of mice develop hematologic malignancy

• most tumors are aggressive T cell lymphomas or leukemias which become disseminated to the spleen

• tumors show the presence of multiple broad DNA copy number gains and losses, with recurrent copy number variation on chromosomes 9 and 15 and overexpression of MRE11 and CHK1

• leukemias contain activating mutation of NOTCH1

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
T-cell acute lymphoblastic leukemia		DOID:5603		J:277750