Phenotypes associated with this allele

• Allele Symbol: Nbn^tm2Zqw
• Allele Name: targeted mutation 2, Zhao-Qi Wang
• Allele ID: MGI:3578645
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Nbn^tm2Zqw/Nbn^tm2Zqw Tg(VAV1-cre)1Graf/0	involves: 129P2/OlaHsd	MGI:6771723
cn2	Nbn^em7Jpt/Nbn^tm2Zqw Tg(VAV1-cre)1Graf/0	involves: 129P2/OlaHsd	MGI:6771693
cn3	Nbn^tm2Zqw/Nbn^tm2Zqw Trp53^tm1Brd/Trp53^tm1Brd Tg(Nes-cre)1Wme/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3579669
cn4	Nbn^tm2Zqw/Nbn^tm2Zqw Trp53^tm1Brd/Trp53^+ Tg(Nes-cre)1Wme/0	involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * CBA	MGI:3579668
cn5	Nbn^tm2Zqw/Nbn^tm2.1Zqw Tg(Nes-cre)1Wme/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3579666
cn6	Nbn^tm2Zqw/Nbn^tm2Zqw Tg(Nes-cre)1Wme/0	involves: 129P2/OlaHsd * C57BL/6 * CBA	MGI:3579667

Genotype
MGI:6771723

cn1

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

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

mortality/aging

postnatal lethality ( J:251434 , J:277750 )

• postnatal lethality due to lack of bone marrow development (J:251434)

• mice succumb at approximately 2 weeks of age to severe anemia (J:277750)

immune system

decreased leukocyte cell number ( J:251434 )

• large decrease in white blood cell count in 12-day-old mice

abnormal bone marrow development ( J:251434 )

• mice exhibit lack of bone marrow development

hematopoietic system

anemia ( J:277750 )

• severe anemia

decreased erythrocyte cell number ( J:251434 )

• large decrease in red blood cell count in 12-day-old mice

decreased leukocyte cell number ( J:251434 )

• large decrease in white blood cell count in 12-day-old mice

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

Genotype
MGI:3579669

cn3

• Allelic Composition: Nbn^tm2Zqw/Nbn^tm2Zqw; Trp53^tm1Brd/Trp53^tm1Brd; Tg(Nes-cre)1Wme/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * CBA

nervous system

nervous system phenotype ( J:98316 )

N • brain weight and cerebellar morphology are normal unlike in mutants with wild-type Trp53

behavior/neurological

behavior/neurological phenotype ( J:98316 )

N • motor coordination defects seen in mutants with wild-type Trp53 are not seen in mutants that are homozygous null for Trp53

neoplasm

increased tumor incidence ( J:98316 )

• similar to other Trp53 null mutations sarcomas and lymphomas are seen; however no cerebellar tumors have been detected

increased lymphoma incidence ( J:98316 )

increased sarcoma incidence ( J:98316 )

Genotype
MGI:3579668

cn4

• Allelic Composition: Nbn^tm2Zqw/Nbn^tm2Zqw; Trp53^tm1Brd/Trp53⁺; Tg(Nes-cre)1Wme/0
• Genetic Background: involves: 129P2/OlaHsd * 129S7/SvEvBrd * C57BL/6 * CBA

nervous system

abnormal cerebellar foliation ( J:98316 )

• foliation structure is improved compared to mutants wild-type for Trp53

abnormal cerebellar granule layer morphology ( J:98316 )

• a marginal increase in granule cell numbers is seen compared to mutants wild-type for Trp53

behavior/neurological

impaired balance ( J:98316 )

• performance on the balance beam test is improved compared to mutants wild-type for Trp53 but is impaired compared to controls and mutants that are homozygous null for Trp53

Genotype
MGI:3579666

cn5

• Allelic Composition: Nbn^tm2Zqw/Nbn^tm2.1Zqw; Tg(Nes-cre)1Wme/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

nervous system

abnormal neuron differentiation ( J:98316 )

• neural stem and progenitor cells from E13.5 brains produce fewer and smaller neurospheres in culture, do not produce secondary neurospheres, and have an increased number of chromosomal breaks per metaphase; however, no increase in apoptosis is seen

• no primary neurospheres were isolated from newborn mutants

absent cerebellar foliation ( J:98316 )

abnormal cerebellum external granule cell layer morphology ( J:98316 )

• at E15.5, E18.5, and P7, proliferation of cells is decreased in the outer external granule cell layer

• at E15.5, E18.5, and P7, apoptosis is increased in the inner external granule cell layer

decreased brain weight ( J:98316 )

• seen at P7

abnormal cerebellar Purkinje cell layer ( J:98316 )

• at P0 the Purkinje cell layer is disorganized

abnormal cerebellar granule layer morphology ( J:98316 )

• at P0 the granule cell layer is disorganized with a reduction in the number of granule cells and ectopic presence of Purkinje cells

small cerebellum ( J:98316 )

• seen at P7-P21

abnormal astrocyte morphology ( J:98316 )

• at P0 the Bergmann glia are abnormal

behavior/neurological

abnormal reflex ( J:98316 )

• when suspended by the tail mutants stretch out their hind limbs

tremors ( J:98316 )

• seen after P7

ataxia ( J:98316 )

• cerebellar ataxia seen after P7

impaired balance ( J:98316 )

• after P7 mutants are unable to complete the balance beam test

akinesia ( J:98316 )

• seen after P7

abnormal gait ( J:98316 )

• seen after P7

increased stereotypic behavior ( J:98316 )

• increased repetitive movements seen after P7

growth/size/body

postnatal growth retardation ( J:98316 )

• detected by P7 and mutants reach only about half of the body weight of control mice at weaning

cellular

abnormal neuron differentiation ( J:98316 )

• neural stem and progenitor cells from E13.5 brains produce fewer and smaller neurospheres in culture, do not produce secondary neurospheres, and have an increased number of chromosomal breaks per metaphase; however, no increase in apoptosis is seen

• no primary neurospheres were isolated from newborn mutants

Genotype
MGI:3579667

cn6

• Allelic Composition: Nbn^tm2Zqw/Nbn^tm2Zqw; Tg(Nes-cre)1Wme/0
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6 * CBA

nervous system

abnormal neuron differentiation ( J:98316 )

• neural stem and progenitor cells from E13.5 brains produce fewer and smaller neurospheres in culture, do not produce secondary neurospheres, and have an increased number of chromosomal breaks per metaphase; however, no increase in apoptosis is seen

• no primary neurospheres were isolated from newborn mutants

absent cerebellar foliation ( J:98316 )

abnormal cerebellum external granule cell layer morphology ( J:98316 )

• at E15.5, E18.5, and P7, proliferation of cells is decreased in the outer external granule cell layer

• at E15.5, E18.5, and P7, apoptosis is increased in the inner external granule cell layer

decreased brain weight ( J:98316 )

• seen at P7

abnormal cerebellar Purkinje cell layer ( J:98316 )

• at P0 the Purkinje cell layer is disorganized

small cerebellum ( J:98316 )

• seen at P7-P21

abnormal astrocyte morphology ( J:98316 )

• at P0 the Bergmann glia are abnormal

behavior/neurological

abnormal involuntary movement ( J:98316 )

• when suspended by the tail mutants stretch out their hind limbs

tremors ( J:98316 )

• seen after P7

ataxia ( J:98316 )

• cerebellar ataxia seen after P7

impaired balance ( J:98316 )

• after P7 mutants are unable to complete the balance beam test

akinesia ( J:98316 )

• seen after P7

abnormal gait ( J:98316 )

• seen after P7

increased stereotypic behavior ( J:98316 )

• increased repetitive movements seen after P7

growth/size/body

postnatal growth retardation ( J:98316 )

• detected by P7 and mutants reach only about half of the body weight of control mice at weaning

cellular

abnormal neuron differentiation ( J:98316 )

• neural stem and progenitor cells from E13.5 brains produce fewer and smaller neurospheres in culture, do not produce secondary neurospheres, and have an increased number of chromosomal breaks per metaphase; however, no increase in apoptosis is seen

• no primary neurospheres were isolated from newborn mutants