Phenotypes associated with this allele

• Allele Symbol: Sh3bp2^tm1Rtpl
• Allele Name: targeted mutation 1, Robert Rottapel
• Allele ID: MGI:3711412
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Sh3bp2^tm1Rtpl/Sh3bp2^tm1Rtpl	B6.129P2-Sh3bp2^tm1Rtpl	MGI:3712169
hm2	Sh3bp2^tm1Rtpl/Sh3bp2^tm1Rtpl	involves: 129P2/OlaHsd * C57BL/6	MGI:5701641

Genotype
MGI:3712169

hm1

• Allelic Composition: Sh3bp2^tm1Rtpl/Sh3bp2^tm1Rtpl
• Genetic Background: B6.129P2-Sh3bp2^tm1Rtpl

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

immune system

increased B cell apoptosis ( J:121380 )

• increased B cell apoptosis in response to stimulation through BCR

decreased B cell proliferation ( J:121380 )

• lower proliferative response following cross-linking with anti-IgM or anti-IgM plus anti-CD40 antibodies

• however, LPS response was normal

decreased pro-B cell number ( J:121380 )

• slight decrease in intermediate pro-B cells (about 32% versus 40% in wild-type)

abnormal B cell number ( J:121380 )

• transitional-2 and mature B cell numbers in the spleen are not affected and the absolute number of B220+ splenocytes is comparable to wild-type

decreased transitional stage B cell number ( J:121380 )

• decrease in the frequency and absolute number of transitional-1 splenic B cells

decreased B-1 B cell number ( J:121380 )

• contraction of the peritoneal B1 B-cell population

abnormal spleen marginal zone morphology ( J:121380 )

• enlargement of the marginal zone compartment in many follicles, as shown by B220+ cell staining, with increased marginal zone (MZ) B cell numbers within compartments

increased marginal zone B cell number ( J:121380 )

• a modest increase in frequency and cell number of marginal zone splenic B cells

decreased immunoglobulin level ( J:121380 )

decreased IgA level ( J:121380 )

decreased IgG1 level ( J:121380 )

• reduction in the levels of IgG1

decreased IgG3 level ( J:121380 )

• reduction in the production of IgG3 antibodies in response to TNP-Ficoll immunization

• however, immune responses to TNP-LPS (TI-1 response) or TNP-Ova (T-dependent response) are normal

decreased IgM level ( J:121380 )

• in response to TNP-Ficoll immunization

abnormal marginal zone B cell physiology ( J:121380 )

• MZ B cells are more susceptible to apoptosis and at and enhanced rate than follicular cells in the same compartment

• MZ B cells have a 2.5-fold increase in Casp3 activation

hematopoietic system

increased B cell apoptosis ( J:121380 )

• increased B cell apoptosis in response to stimulation through BCR

decreased B cell proliferation ( J:121380 )

• lower proliferative response following cross-linking with anti-IgM or anti-IgM plus anti-CD40 antibodies

• however, LPS response was normal

decreased pro-B cell number ( J:121380 )

• slight decrease in intermediate pro-B cells (about 32% versus 40% in wild-type)

abnormal B cell number ( J:121380 )

• transitional-2 and mature B cell numbers in the spleen are not affected and the absolute number of B220+ splenocytes is comparable to wild-type

decreased transitional stage B cell number ( J:121380 )

• decrease in the frequency and absolute number of transitional-1 splenic B cells

decreased B-1 B cell number ( J:121380 )

• contraction of the peritoneal B1 B-cell population

abnormal spleen marginal zone morphology ( J:121380 )

• enlargement of the marginal zone compartment in many follicles, as shown by B220+ cell staining, with increased marginal zone (MZ) B cell numbers within compartments

increased marginal zone B cell number ( J:121380 )

• a modest increase in frequency and cell number of marginal zone splenic B cells

decreased immunoglobulin level ( J:121380 )

decreased IgA level ( J:121380 )

decreased IgG1 level ( J:121380 )

• reduction in the levels of IgG1

decreased IgG3 level ( J:121380 )

• reduction in the production of IgG3 antibodies in response to TNP-Ficoll immunization

• however, immune responses to TNP-LPS (TI-1 response) or TNP-Ova (T-dependent response) are normal

decreased IgM level ( J:121380 )

• in response to TNP-Ficoll immunization

abnormal marginal zone B cell physiology ( J:121380 )

• MZ B cells are more susceptible to apoptosis and at and enhanced rate than follicular cells in the same compartment

• MZ B cells have a 2.5-fold increase in Casp3 activation

cellular

increased B cell apoptosis ( J:121380 )

• increased B cell apoptosis in response to stimulation through BCR

decreased B cell proliferation ( J:121380 )

• lower proliferative response following cross-linking with anti-IgM or anti-IgM plus anti-CD40 antibodies

• however, LPS response was normal

Genotype
MGI:5701641

hm2

• Allelic Composition: Sh3bp2^tm1Rtpl/Sh3bp2^tm1Rtpl
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

hematopoietic system

abnormal macrophage physiology ( J:221901 )

• LPS-induced actin polymerization is diminished in peritoneal macrophages but not in dendritic cells

• bone marrow-derived macrophages are impaired in their capacity to differentiate into multinucleated osteoclasts

impaired macrophage phagocytosis ( J:221901 )

• in vivo E. coli clearance is less efficient in mutants, indicating impaired phagocytosis

• bone marrow-derived macrophages are ineffective in phagocyting latex beads

homeostasis/metabolism

abnormal circulating cytokine level ( J:221901 )

• mice exhibit reduced levels of inflammatory cytokines (IL-6, IL-12p70 and TNF-alpha) in the serum in response to LPS challenge compared to wild-type mice

immune system

abnormal macrophage physiology ( J:221901 )

• LPS-induced actin polymerization is diminished in peritoneal macrophages but not in dendritic cells

• bone marrow-derived macrophages are impaired in their capacity to differentiate into multinucleated osteoclasts

impaired macrophage phagocytosis ( J:221901 )

• in vivo E. coli clearance is less efficient in mutants, indicating impaired phagocytosis

• bone marrow-derived macrophages are ineffective in phagocyting latex beads

abnormal circulating cytokine level ( J:221901 )

• mice exhibit reduced levels of inflammatory cytokines (IL-6, IL-12p70 and TNF-alpha) in the serum in response to LPS challenge compared to wild-type mice

abnormal interleukin-6 secretion ( J:221901 )

• cytochalasin B treatment decreases IL-6 production by LPS-stimulated macrophages more than in wild-type macrophages

• treatment with the actin-polymerizing agent jasplakinolide restores normal IL-6 secretion by LPS-stimulated bone marrow-derived macrophages

decreased tumor necrosis factor secretion ( J:221901 )

• bone marrow-derived macrophages challenged with PAMP:LPS, CpG oligodeoxynucleotide (CpG ODN) or zymosan depleted of TLR-stimulating properties show reduced TNF-alpha production in the supernatant

• however, LPS-stimulated bone marrow-derived dendritic cells produce similar levels of IL-12p70 as wild-type cells

cellular

impaired macrophage phagocytosis ( J:221901 )

• in vivo E. coli clearance is less efficient in mutants, indicating impaired phagocytosis

• bone marrow-derived macrophages are ineffective in phagocyting latex beads