Phenotypes associated with this allele

• Allele Symbol: Igha^tm1Grh
• Allele Name: targeted mutation 1, Gregory Harriman
• Allele ID: MGI:1857185
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Igha^tm1Grh/Igha^tm1Grh	involves: 129 * C57BL/6	MGI:3834168
hm2	Igha^tm1Grh/Igha^tm1Grh	involves: 129S7/SvEvBrd * C57BL/6	MGI:3834142
cx3	Igha^tm1Grh/Igha^tm1Grh Tg(Tnfsf13b)1Fma/Tg(Tnfsf13b)1Fma	involves: 129S7/SvEvBrd * C57BL/6 * DBA/2	MGI:5300899

Genotype
MGI:3834168

hm1

• Allelic Composition: Igha^tm1Grh/Igha^tm1Grh
• Genetic Background: involves: 129 * C57BL/6

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

immune system

increased susceptibility to parasitic infection ( J:74568 , J:140515 )

• mice fail to clear a Giardia muris infection (J:74568)

• like wild-type mice, these mice began to reduce Giardia numbers in the gut 3 weeks after infection but mice then fail to clear the infection with parasite numbers instead increasing (J:74568)

• mice have 100-fold higher Giardia trophozoite numbers in the gut 7 week after infection compared to controls with an accompanying 10-fold higher cyst stool output (J:74568)

• mice continue to shed cysts in the stool over at least 4 months (J:74568)

• mice are better at fighting the Giardia infection than Igh-6^tm1Cgn homozygotes, with a 21-fold reduction in peak trophozoite number 7 weeks post-infection compared to a 2-fold reduction (J:74568)

• mice are not protected from Giardia upon a secondary challenge as wild-type mice are (J:74568)

• mice also fail to clear the Giardia lamblia strain that causes sickness in humans (J:74568)

• mice are more susceptible to Giardia muris infection compared to controls (J:140515)

• seven weeks after infection, mice have over 1,000-fold higher trophozoite numbers in the small intestine compared with controls (J:140515)

• mice are also more susceptible to infection with the GS/M strain of G. lamblia that also infects humans (J:140515)

Genotype
MGI:3834142

hm2

• Allelic Composition: Igha^tm1Grh/Igha^tm1Grh
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

cellular

decreased T cell proliferation ( J:125472 )

• splenocytes have decreased proliferation in response to the T cell mitogen PHA that can be restored by the addition of IL-12

immune system

immune system phenotype ( J:53218 )

N • mice immunized with an influenza subunit vaccine in the presence of cholera toxin B subunit or whole cholera toxin are protected against subsequent influenza virus infection in the same manner as controls

abnormal immunoglobulin level ( J:125472 )

decreased IgA level ( J:53217 , J:125472 )

• IgA levels are completely absent in the serum and nasal, pulmonary, and gastrointestinal secretions (J:53217)

• there is no detectable IgA in these mice (J:125472)

decreased IgE level ( J:53217 )

• IgE levels are decreased more than twenty-fold compared to controls in both the serum and pulmonary secretions

decreased IgG3 level ( J:53217 )

• IgG3 levels are decreased about seven-fold in the serum and five-fold in intestinal secretions

• IgG3 levels are decreased about ten-fold in nasal secretions and three- to four- fold in pulmonary secretions

increased IgG level ( J:53217 )

• IgG levels are about two times higher than controls in the serum and three times higher in the intestine

increased IgG1 level ( J:53217 , J:125472 )

• there is a two-fold increase of IgG1 levels in the serum and a five-fold increase in the intestine (J:53217)

• influenza-vaccinated mice have increased serum levels of antigen-specific IgG1 compared to controls (J:125472)

increased IgG2a level ( J:53217 )

• IgG2a is increased about two-fold in intestinal secretions

increased IgG2b level ( J:53217 )

• there is a two-fold increase in IgG2b levels in pulmonary secretions

increased IgM level ( J:53217 , J:125472 )

• IgM levels in the serum are about double the amount found in wild-type controls (J:53217)

• IgM levels in intestinal secretions is about 25 times higher than in controls (J:53217)

• mice immunized with an influenza vaccine + IL-12 have increased serum levels of antigen-specific IgM compared to controls (J:125472)

abnormal T cell activation ( J:53217 )

• the stimulative response of splenocytes to PHA mitogen is almost half that of controls

decreased T cell proliferation ( J:125472 )

• splenocytes have decreased proliferation in response to the T cell mitogen PHA that can be restored by the addition of IL-12

abnormal memory T cell physiology ( J:125472 )

• T cells purified from vaccinated mice fail to respond to vaccinated antigen when cultured in vitro with wild-type antigen presenting cells

abnormal dendritic cell physiology ( J:125472 )

• dendritic cells fail to activate primed wild-type T cells when co-cultured in the presence of antigen

• inclusion of IL-12 can rescue this defect

decreased interferon-gamma secretion ( J:53217 )

• IFN-gamma secretion by activated splenocytes is significantly less than controls

increased interferon-gamma secretion ( J:125472 )

• splenocytes have increased secretion of IFN-gamma when incubated with the T cell mitogen PHA and IL-12

increased interleukin-4 secretion ( J:53217 )

• IL-4 secretion by unstimulated splenocytes is enhanced compared to controls

• stimulated splenocytes produce the same amout of IL-4 as controls

increased susceptibility to Orthomyxoviridae infection ( J:125472 )

• intranasal vaccination with H1N1 protein in the absence of adjuvant fails to protect these mice with only a 13% survival when subsequently challenged with influenza compared to 75% survival for controls

• survival rates can be rescued by including IL-12 as an adjuvant in the vaccination

hematopoietic system

abnormal immunoglobulin level ( J:125472 )

decreased IgA level ( J:53217 , J:125472 )

• IgA levels are completely absent in the serum and nasal, pulmonary, and gastrointestinal secretions (J:53217)

• there is no detectable IgA in these mice (J:125472)

decreased IgE level ( J:53217 )

• IgE levels are decreased more than twenty-fold compared to controls in both the serum and pulmonary secretions

decreased IgG3 level ( J:53217 )

• IgG3 levels are decreased about seven-fold in the serum and five-fold in intestinal secretions

• IgG3 levels are decreased about ten-fold in nasal secretions and three- to four- fold in pulmonary secretions

increased IgG level ( J:53217 )

• IgG levels are about two times higher than controls in the serum and three times higher in the intestine

increased IgG1 level ( J:53217 , J:125472 )

• there is a two-fold increase of IgG1 levels in the serum and a five-fold increase in the intestine (J:53217)

• influenza-vaccinated mice have increased serum levels of antigen-specific IgG1 compared to controls (J:125472)

increased IgG2a level ( J:53217 )

• IgG2a is increased about two-fold in intestinal secretions

increased IgG2b level ( J:53217 )

• there is a two-fold increase in IgG2b levels in pulmonary secretions

increased IgM level ( J:53217 , J:125472 )

• IgM levels in the serum are about double the amount found in wild-type controls (J:53217)

• IgM levels in intestinal secretions is about 25 times higher than in controls (J:53217)

• mice immunized with an influenza vaccine + IL-12 have increased serum levels of antigen-specific IgM compared to controls (J:125472)

abnormal T cell activation ( J:53217 )

• the stimulative response of splenocytes to PHA mitogen is almost half that of controls

decreased T cell proliferation ( J:125472 )

• splenocytes have decreased proliferation in response to the T cell mitogen PHA that can be restored by the addition of IL-12

abnormal memory T cell physiology ( J:125472 )

• T cells purified from vaccinated mice fail to respond to vaccinated antigen when cultured in vitro with wild-type antigen presenting cells

Genotype
MGI:5300899

cx3

• Allelic Composition: Igha^tm1Grh/Igha^tm1Grh; Tg(Tnfsf13b)1Fma/Tg(Tnfsf13b)1Fma
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6 * DBA/2

immune system

immune system phenotype ( J:178227 )

N • double mutant do not exhibit the impaired kidney function seen in single Tg(Tnfsf13b)1Fma homozygotes and have reduced levels of serum IgA and IgA deposits in the kidney, and reduced hematuria, urinary protein and albumin levels indicating that IgA is important for renal disease development in Tg(Tnfsf13b)1Fma homozygotes