mortality/aging
| N |
• mice exhibit normal survival following diethylnitrosamine (DEN) challenged
(J:173666)
|
|
cn1
|
Adh5tm1.1Llli/Adh5tm1.1Llli Tg(Vav1-cre)A2Kio/0 B6.Cg-Adh5tm1.1Llli Tg(Vav1-cre)A2Kio |
|
|||||||||||||||||
| N |
• mice exhibit normal survival following diethylnitrosamine (DEN) challenged
(J:173666)
|
|
cn2
|
Cdkn1atm1Led/Cdkn1atm1Led Zbtb17tm1Cksn/Zbtb17tm1Cksn Tg(Vav1-cre)A2Kio/0 B6.Cg-Zbtb17tm1Cksn Cdkn1atm1Led Tg(Vav1-cre)A2Kio |
|
|||||||||||||||||
|
• double negative to double positive differentiation is blocked unlike in wild-type mice
|
|
• double negative to double positive differentiation is blocked unlike in wild-type mice
|
|
• double negative to double positive differentiation is blocked unlike in wild-type mice
|
|
cn3
|
Zbtb17tm1Cksn/Zbtb17tm1Cksn Tg(Vav1-cre)A2Kio/0 B6.Cg-Zbtb17tm1Cksn Tg(Vav1-cre)A2Kio |
|
|||||||||||||||||
|
• pro-T cells exhibit excessive cell death unlike wild-type cells
|
|
• early lymphoid progenitors and early thymic precursors fail to differentiate into mature T cells in the presence of Il7 unlike in wild-type mice
• however, inhibition of SOCS1 or overexpression of Bcl2 restores T cell differentiation in vitro
|
|
• alphabeta-T cells are reduced 1000-fold compared to in wild-type mice
|
|
• early T-cell precursors in the thymus are reduced compared to in wild-type mice
|
|
• DN1a-e subsets are decreased 70- to 130-fold compared to in wild-type mice
• DN1a/b cells are decreased 230-fold compared to in wild-type mice
|
|
• 100-fold reduction in DN2a cells
• 40-fold reduction in DN2b cells
|
|
• 3-fold reduction in DN3a cells
• 10-fold reduction in DN3b cells
|
|
• 7-fold
|
|
• 100-fold reduction in cellularity
|
|
• early lymphoid progenitors and early thymic precursors fail to differentiate into mature T cells in the presence of Il7 unlike in wild-type mice
• however, inhibition of SOCS1 or overexpression of Bcl2 restores T cell differentiation in vitro
|
|
• alphabeta-T cells are reduced 1000-fold compared to in wild-type mice
|
|
• early T-cell precursors in the thymus are reduced compared to in wild-type mice
|
|
• DN1a-e subsets are decreased 70- to 130-fold compared to in wild-type mice
• DN1a/b cells are decreased 230-fold compared to in wild-type mice
|
|
• 100-fold reduction in DN2a cells
• 40-fold reduction in DN2b cells
|
|
• 3-fold reduction in DN3a cells
• 10-fold reduction in DN3b cells
|
|
• 7-fold
|
|
• 100-fold reduction in cellularity
|
|
• pro-T cells exhibit excessive cell death unlike wild-type cells
|
|
• early T-cell precursors in the thymus are reduced compared to in wild-type mice
|
|
• DN1a-e subsets are decreased 70- to 130-fold compared to in wild-type mice
• DN1a/b cells are decreased 230-fold compared to in wild-type mice
|
|
• 100-fold reduction in DN2a cells
• 40-fold reduction in DN2b cells
|
|
• 3-fold reduction in DN3a cells
• 10-fold reduction in DN3b cells
|
|
• early lymphoid progenitors and early thymic precursors fail to differentiate into mature T cells in the presence of Il7 unlike in wild-type mice
• however, inhibition of SOCS1 or overexpression of Bcl2 restores T cell differentiation in vitro
|
|
cn4
|
Suv420h1tm1Jnw/Suv420h1tm1Jnw Suv420h2tm1.1Jnw/Suv420h2tm1.1Jnw Tg(Vav1-cre)A2Kio/0 involves: 129/Sv * C57BL/6J * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
| N |
• V(D)J recombination in B and T cells is normal
(J:139510)
|
|
• in a competitive reconstitution assay, cells fail to repopulate the B and T cell population as well as do wild type cells
|
|
• fewer cells undergo the switch from IgM to IgG1 or IgG3 compared to in wild type mice
• however, there is no increase in Igh chromosomal aberrations
|
|
• in the thymus
|
|
• the number of mature and re-circulating B cells is decreased compared to in wild-type mice
• however, the numbers of pro- and pre-B cells is normal
|
|
• in a competitive reconstitution assay, cells fail to repopulate the B and T cell population as well as do wild type cells
|
|
• fewer cells undergo the switch from IgM to IgG1 or IgG3 compared to in wild type mice
• however, there is no increase in Igh chromosomal aberrations
|
|
• in the thymus
|
|
• the number of mature and re-circulating B cells is decreased compared to in wild-type mice
• however, the numbers of pro- and pre-B cells is normal
|
|
• in a competitive reconstitution assay, cells fail to repopulate the B and T cell population as well as do wild type cells
|
|
• fewer cells undergo the switch from IgM to IgG1 or IgG3 compared to in wild type mice
• however, there is no increase in Igh chromosomal aberrations
|
|
• in the thymus
|
|
cn5
|
Dhx36tm1.2Pmt/Dhx36tm1.2Pmt Tg(Vav1-cre)A2Kio/0 involves: 129P2/Ola * 129S4/SvJaeSor * C57BL/6 * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
|
• mice exhibit an increase in ProE and Ery.A fractions but a decrease in Ery.B and Ery.C in the bone marrow compared with control mice
• mice exhibit an increase in ProE and Ery.A fractions but a decrease in Ery.C in the spleen compared with control mice
• early erythropoiesis is partially blocked in association with a cell cycle defect
• proerythroblast exhibit reduced proliferation compared with control cells
• however, proerythroblast apoptosis rates are normal
|
|
• ProE cells are increased 3.6- and 74-fold in the bone marrow and spleen compared with control mice
|
|
• in the bone marrow
|
|
• 4.7-fold in the spleen
|
|
• secondary
|
|
• decrease in the granulocyte macrophage progenitor (GMP) cells in the bone marrow
• increase in the megakaryocyte-erythroid progenitor (MEP) cells in the spleen
|
|
• decrease in the granulocyte macrophage progenitor (GMP) cells in the bone marrow
|
|
• early long and short term hematopoietic stem cells are increased compared to in control mice
• however, the number of lymphoid-primed multipotent progenitors is normal and the increased in hematopoietic stem cells disappears in the alter stages of differentiation
|
|
• in adult mice
|
|
• without affecting architecture
|
|
• reduced half-life
|
|
• in adult mice
|
|
• proerythroblast exhibit reduced proliferation compared with control cells
|
|
• in adult mice
|
|
• without affecting architecture
|
|
cn6
|
Tcf3tm1Mbu/Tcf3tm1Mbu Tg(Ikzf1-Tcfe2a,GFP)1Mbu/0 Tg(Vav1-cre)A2Kio/0 involves: 129P2/OlaHsd * C57BL * CBA |
|
|||||||||||||||||
| N |
• c-Kit+B220+ pro-B cells and c-Kit-B220+ developmental stages are rescued
(J:137719)
|
|
cn7
|
Tcf3tm1Mbu/Tcf3tm1Mbu Tg(Vav1-cre)A2Kio/0 involves: 129P2/OlaHsd * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
|
• mice lack committed c-Kit+CD19+ pro-B cells
|
|
• mice lack committed c-Kit+CD19+ pro-B cells
|
|
• mice lack committed c-Kit+CD19+ pro-B cells
|
|
cn8
|
Ikzf1tm1.1(Pax5)Mbu/Ikzf1+ Tcf3tm1Mbu/Tcf3tm1Mbu Tg(Vav1-cre)A2Kio/0 involves: 129P2/OlaHsd * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
| N |
• development of pro-B cells is rescued
(J:137719)
|
|
• proximal VH7183-DJH and distal VHJ558-DJH rearrangements of the IgH are reduced compared to in wild-type mice
• Vk-Jk recombination of the Igk locus is absent
|
|
• proximal VH7183-DJH and distal VHJ558-DJH rearrangements of the IgH are reduced compared to in wild-type mice
• Vk-Jk recombination of the Igk locus is absent
|
|
• proximal VH7183-DJH and distal VHJ558-DJH rearrangements of the IgH are reduced compared to in wild-type mice
• Vk-Jk recombination of the Igk locus is absent
|
|
cn9
|
Rbpjtm1Hon/Rbpjtm1Hon Tg(Vav1-cre)A2Kio/0 involves: 129P2/OlaHsd * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
|
• transplanted bone marrow progenitors transfected with BCR-ABL and NUP98-HOXA9 proliferate slower than similarly treated wild-type cells improving host survival
|
|
cn10
|
Idh1tm1Mak/Idh1tm1Mak Tg(Vav1-cre)A2Kio/0 involves: 129P2/OlaHsd * C57BL/6 * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
| N |
• mice exhibit normal hematopoietical parameters in peripheral blood and normal bone marrow cell numbers
(J:186700)
|
|
• increase in common lymphocyte progenitor cells in the bone marrow and spleen
|
|
• increase in megakaryocyte-erythroid progenitors in the spleen
|
|
• increase in LSK and lineage-restricted progenitors in the bone marrow and spleen
• increase in LK in the spleen
|
|
• increase in megakaryocyte-erythroid progenitors in the spleen
|
|
cn11
|
Myd88tm1Defr/Myd88tm1Defr Tg(Vav1-cre)A2Kio/0 involves: 129P2/OlaHsd * C57BL/6 * SJL |
|
|||||||||||||||||
|
• NK cells fail to make IFN-gamma in response to injections of TLR9 agonists
• NK cells in vivo have a blunted IFN-gamma response to LPS injections
|
|
cn12
|
Syktm1.1Nns/Syktm1.1Nns Tg(Tie1-cre)9Ref/0 Tg(Vav1-cre)A2Kio/0 involves: 129S1/Sv * 129X1/SvJ * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
| N |
• unlike null homozygotes, mice survive to adulthood
(J:181715)
|
|
• at E14.5, mice exhibit blood-filled vessels unlike wild-type mice
|
|
cn13
|
Mll1tm1Brad/Mll1tm1Brad Tg(Vav1-cre)A2Kio/? involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
|
• there is about a 3-fold reduction in pre-B cell CFUs isolated from bone marrow
|
|
• there is about a 2-fold reduction in myeloid CFU number isolated from E13.5 fetal livers
• a similar reduction in CFU is observed with bone marrow cells
|
|
• mutant HSC bone marrow cells give less then a 1% long-term reconstitution when transplanted at a 1:1 ratio with wild-type bone marrow into irradiated mice
• mutant HSC bone marrow cells give only a 2% long-term reconstitution when transplanted at a 10:1 ratio
• poor reconstitution is observable as little as 4 weeks after transfer
|
|
• there is about a 3-fold reduction in pre-B cell CFUs isolated from bone marrow
|
|
• there is about a 3-fold reduction in pre-B cell CFUs isolated from bone marrow
|
|
cn14
|
Rr7tm3.1Kio/Rr7+ Tg(Vav1-cre)A2Kio/0 involves: 129S4/SvJae * C57BL/6 * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
| N |
• mice exhibit normal expression of Cd8a and Cd8b
(J:179326)
|
|
cn15
|
Kitltm2.1Sjm/Kitltm2.2Sjm Tg(Vav1-cre)A2Kio/0 involves: BALB/cJ * C57BL * CBA/Ca * SJL |
|
|||||||||||||||||
| N |
• exhibit normal blood cell counts, bone marrow composition, bone marrow and spleen cellularity, and reconstitution capacity
(J:180431)
|
|
• 2-fold as in Kitltm2.2Sjm heterozygotes in the bone marrow
|
|
cn16
|
Syktm1.1Nns/Syktm1.1Nns Tg(Vav1-cre)A2Kio/0 involves: C57BL/10 * CBA/Ca |
|
|||||||||||||||||
| N |
• unlike null homozygotes, mice survive to adulthood
(J:181715)
|
|
• at E14.5, mice exhibit blood-filled vessels unlike control mice
• at 8 weeks, dye injection confirms interconnection between lymphatic and blood vessels with rapid spread labeling unlike in control mice
|
|
• at 8 weeks, dye injection confirms interconnection between lymphatic and blood vessels with rapid spread labeling unlike in control mice
|
|
cn17
|
Tg(Kit*D814V)1Roer/0 Tg(Vav1-cre)A2Kio/0 involves: C57BL/6 * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
|
• similar to the phenotype in mice carrying Tg(CMV-cre)1Cgn and Tg(Kit*D814V)1Roer
|
|
cn18
|
Tg(Kit*D814V)3Roer/0 Tg(Vav1-cre)A2Kio/0 involves: C57BL/6 * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
|
• similar to the phenotype in mice carrying Tg(CMV-cre)1Cgn and Tg(Kit*D814V)3Roer
|
|
cn19
|
Idh1tm2Mak/Idh1tm2Mak Tg(Vav1-cre)A2Kio/0 involves: C57BL/6 * C57BL/10 * CBA/Ca |
|
|||||||||||||||||
| N |
• mice exhibit normal hematopoietical parameters in peripheral blood and normal bone marrow cell numbers
(J:186700)
|
|
• increase in common lymphocyte progenitor cells in the bone marrow and spleen
|
|
• increase in megakaryocyte-erythroid progenitors in the spleen
|
|
• increase in LSK and lineage-restricted progenitors in the bone marrow and spleen
• increase in LK in the spleen
|
|
• increase in megakaryocyte-erythroid progenitors in the spleen
|
|
cn20
|
Rc3h1tm1.1Mass/Rc3h1tm1.1Mass Tg(Vav1-cre)A2Kio/0 involves: C57BL/6 * C57BL/10 * CBA/Ca * NZB * SJL |
|
|||||||||||||||||
| N |
• mice exhibit normal T cell development and autoimmunity
(J:177784)
|
|
• in the bone marrow
|
|
• immature and re-circulating B cells
|
|
• in the spleen
|
|
• in the spleen
|
|
• in the spleen
|
|
• increased numbers in the spleen
|
|
• 1.5-fold but not as severe as in Rc3h1san homozygotes
|
|
• 1.5-fold
|
|
• 1.5-fold
|
|
• some are disrupted
|
|
• 1.5-fold
|
|
• mice exhibit increased spontaneous germinal center formation compared with control mice
|
|
• in the bone marrow
|
|
• in the bone marrow
|
|
• immature and re-circulating B cells
|
|
• in the spleen
|
|
• in the spleen
|
|
• in the spleen
|
|
• increased numbers in the spleen
|
|
• 1.5-fold but not as severe as in Rc3h1san homozygotes
|
|
• 1.5-fold
|
|
• 1.5-fold
|
|
• some are disrupted
|
|
• 1.5-fold
|
|
cn21
|
Atg7tm1Tchi/Atg7tm1Tchi Tg(Vav1-cre)A2Kio/0 involves: C57BL/6NCrlj * C57BL/10 * CBA/Ca * CBA/JNCrlj |
|
|||||||||||||||||
|
• reduction in most myeloid progenitors
• numbers of myeloid subsets CD11b+Gr1- and CD11b-Gr1+ are reduced in blood and decrease further over time
|
|
• numbers of CD11b+Gr1+ cells are increased in the blood at 5 and 6 weeks of age but then decrease to below wild-type levels at 8 weeks of age
• CD11b+Gr1+ cells in the spleen and bone marrow are increased and show higher proliferation rates
• mutants exhibit presence of atypical myeloid infiltrates in a wide range of organs
|
|
• mutants are cytopenic for all blood leukocyte populations except for CD11b+Gr1+ cells
|
|
• absolute cell counts of B cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
|
• immature NK cells (Lin-CD3-CD122+NK1.1+DX5+) are depleted in the bone marrow
• absolute cell counts of NK cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
|
• absolute cell counts of T cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
|
• common lymphoid progenitors (Lin-Flt3HighIL7RaHighSca-1Lowc-KitLow) are reduced in mutants
• numbers of CCR9+ lymphoid-primed multipotent progenitors are reduced in the bone marrow of mutants
|
|
• overall bone marrow cell count is reduced
|
|
• mutant LSK (Lin-Sca-1+c-Kit+) cells accumulate mitochondria, mitochondrial superoxide, and DNA damage and exhibit increased levels of apoptosis and proliferation
|
|
• numbers of hematopoietic stem cells are reduced in all mutants, regardless of disease progression
• absolute numbers of LSK (Lin-Sca-1+c-Kit+) cells significantly increased in asymptomatic 7 week old mutants, however as they develop symptoms, the frequency of LSK cells falls to wild-type levels
• the Lin-Sca-1-c-Kit+ (LK) compartment, containing more mature hematopoietic progenitors, is decreased
|
|
• adult bone marrow cells from mutants transplanted together with CD45.1+ wild-type bone marrow cells into lethally irradiated wild-type hosts fail to contribute to reconstitution of cells in the hosts while in noncompetitive reconstitution experiments, lethally irradiated mice die within 4 weeks after transplantation with mutant bone marrow cells, indicating loss of hematopoietic stem cell activity
|
|
• numbers of CD11b+Gr1+ cells are increased in the blood at 5 and 6 weeks of age but then decrease to below wild-type levels at 8 weeks of age
• CD11b+Gr1+ cells in the spleen and bone marrow are increased and show higher proliferation rates
• mutants exhibit presence of atypical myeloid infiltrates in a wide range of organs
|
|
• mutants are cytopenic for all blood leukocyte populations except for CD11b+Gr1+ cells
|
|
• absolute cell counts of B cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
|
• immature NK cells (Lin-CD3-CD122+NK1.1+DX5+) are depleted in the bone marrow
• absolute cell counts of NK cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
|
• absolute cell counts of T cells are decreased in the peripheral blood of mutants and numbers drop steadily over time
|
|
• common lymphoid progenitors (Lin-Flt3HighIL7RaHighSca-1Lowc-KitLow) are reduced in mutants
• numbers of CCR9+ lymphoid-primed multipotent progenitors are reduced in the bone marrow of mutants
|
Mouse Models of Human Disease |
OMIM ID | Ref(s) | |
| Myelodysplastic Syndrome; MDS | 614286 | J:176843 | |