Phenotypes associated with this allele

• Allele Symbol: Zbtb7a^tm1Ppp
• Allele Name: targeted mutation 1, Pier Paolo Pandolfi
• Allele ID: MGI:3711162
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Zbtb7a^tm1Ppp/Zbtb7a^tm1Ppp	B6.129S1-Zbtb7a^tm1Ppp	MGI:3711413
cn2	Zbtb7a^tm1Ppp/Zbtb7a^tm2Ppp Tg(Mx1-cre)1Cgn/0	involves: 129S1/Sv * C57BL/6 * CBA	MGI:3711414

Genotype
MGI:3711413

hm1

• Allelic Composition: Zbtb7a^tm1Ppp/Zbtb7a^tm1Ppp
• Genetic Background: B6.129S1-Zbtb7a^tm1Ppp

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

mortality/aging

lethality throughout fetal growth and development, complete penetrance ( J:121576 )

• lethality occurs at 16.5 days post coitum (dpc)

hematopoietic system

hematopoietic system phenotype ( J:121576 )

N • hematopoietic stem cell (HSC) and common lyphoid progenitor (CLP) populations are normal

abnormal lymphopoiesis ( J:121576 )

• abnormal in fetal liver at 14.5 dpc

decreased pro-B cell number ( J:121576 )

• pro-B cells are barely detectable in interleukin 7-treated cultures of fetal liver HSCs compared to wild-type cultures

decreased B cell number ( J:121576 )

• at 14.5 dpc, total number of CD19+B220+ B cells is reduced

immune system

abnormal lymphopoiesis ( J:121576 )

• abnormal in fetal liver at 14.5 dpc

decreased pro-B cell number ( J:121576 )

• pro-B cells are barely detectable in interleukin 7-treated cultures of fetal liver HSCs compared to wild-type cultures

decreased B cell number ( J:121576 )

• at 14.5 dpc, total number of CD19+B220+ B cells is reduced

abnormal response to transplant ( J:121576 )

• when fetal liver cells are transplanted into irradiated recipients for bone marrow competitive repopulation assays, B cells derived from mutant livers are nearly undetectable in peripheral blood

Genotype
MGI:3711414

cn2

• Allelic Composition: Zbtb7a^tm1Ppp/Zbtb7a^tm2Ppp; Tg(Mx1-cre)1Cgn/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * CBA

hematopoietic system

abnormal B cell differentiation ( J:121576 )

• with pIpC treatement, B cell development in bone marrow is severely impaired; pro-B, pre-B, and immunoglobulin IgM+ B cells are drastically reduced in number, whereas prepro-B cell numbers are increased with pIpC treatment

• prepro-B cells express elevated levels of T cell-specific target genes and appear to aberrantly committed to the T cell lineage despite B220 expression; in culture, pIpC-treated cells lose B220 expression and differentiate into CD4/8 double positive T cells

• inhibition of Notch signaling by treatment with a gamma secretase inhibitor (GSI) rescues B or T cell commitment abnormalities

abnormal double-positive T cell morphology ( J:121576 )

• accumulation of extrathymic double-positive T cells is seen in bone marrow of pIpC treated mice, with these cells accounting for ~30% of bone marrow mononuclear cells 1 month after pIpC treatment; these DP T cells are not found in spleen or Peyer's patches

decreased leukocyte cell number ( J:121576 )

• after injection of polyinosinic:polycytidylic acid (pIpC) at 2 week intervals starting at 3 weeks of age to induce cre expression, significant decline in white blood cells is observed relative to untreated controls

decreased B cell number ( J:121576 )

• reduction in B220+ B cells with polyinosinic:polycytidylic acid-induced cre induction

• however, T cell numbers remain similar to controls

increased hematopoietic stem cell number ( J:121576 )

• with pIpC treatment, slightly increased numbers are observed with pIpC treatment; numbers of common lyphoid progenitor (CLP) cells are also slightly elevated

immune system

immune system phenotype ( J:121576 )

N • slight decrease in double-negative 3 (DN3) and double-negative 4 (DN4) thymocyte populations is seen, but proportions of CD4 single-positive, CD8 single-positive, and CD4/8 double-positive T cells are comparable to control mice after pIpC treatment

abnormal B cell differentiation ( J:121576 )

• with pIpC treatement, B cell development in bone marrow is severely impaired; pro-B, pre-B, and immunoglobulin IgM+ B cells are drastically reduced in number, whereas prepro-B cell numbers are increased with pIpC treatment

• prepro-B cells express elevated levels of T cell-specific target genes and appear to aberrantly committed to the T cell lineage despite B220 expression; in culture, pIpC-treated cells lose B220 expression and differentiate into CD4/8 double positive T cells

• inhibition of Notch signaling by treatment with a gamma secretase inhibitor (GSI) rescues B or T cell commitment abnormalities

abnormal double-positive T cell morphology ( J:121576 )

• accumulation of extrathymic double-positive T cells is seen in bone marrow of pIpC treated mice, with these cells accounting for ~30% of bone marrow mononuclear cells 1 month after pIpC treatment; these DP T cells are not found in spleen or Peyer's patches

decreased leukocyte cell number ( J:121576 )

• after injection of polyinosinic:polycytidylic acid (pIpC) at 2 week intervals starting at 3 weeks of age to induce cre expression, significant decline in white blood cells is observed relative to untreated controls

decreased B cell number ( J:121576 )

• reduction in B220+ B cells with polyinosinic:polycytidylic acid-induced cre induction

• however, T cell numbers remain similar to controls

abnormal response to transplant ( J:121576 )

• when cells from these mice are transferred to lethally irradiated recipients, upon pIpC treatment, donor-derived double positive T cells accumulate in bone marrow and peripheral blood