Phenotypes associated with this allele

• Allele Symbol: Grk2^tm1Gwd
• Allele Name: targeted mutation 1, Gerald W Dorn II
• Allele ID: MGI:3763199
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Grk2^tm1Gwd/Grk2^tm1Gwd	involves: 129S4/SvJaeSor	MGI:3763208
cn2	Grk2^tm1Gwd/Grk2^tm1Gwd Cd79a^tm1(cre)Reth/Cd79a^+	involves: 129 * BALB/c * C57BL/6	MGI:5295055
cn3	Grk2^tm1Gwd/Grk2^tm1Mca Tg(Cd4-cre)1Cwi/0	involves: 129 * C57BL/6 * DBA/2	MGI:5295054
cn4	Grk2^tm1Gwd/Grk2^tm1Gwd Nkx2-5^tm1(cre)Rjs/Nkx2-5^+	involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6	MGI:3763210

Genotype
MGI:3763208

hm1

• Allelic Composition: Grk2^tm1Gwd/Grk2^tm1Gwd
• Genetic Background: involves: 129S4/SvJaeSor

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

normal phenotype

no abnormal phenotype detected ( J:126501 )

• mice are equivalent to wild-type mice and used as controls

Genotype
MGI:5295055

cn2

• Allelic Composition: Grk2^tm1Gwd/Grk2^tm1Gwd; Cd79a^tm1(cre)Reth/Cd79a⁺
• Genetic Background: involves: 129 * BALB/c * C57BL/6

immune system

decreased B cell number ( J:176118 )

• in the lymph nodes

increased B cell number ( J:176118 )

• in the spleen and blood

increased follicular B cell number ( J:176118 )

increased marginal zone B cell number ( J:176118 )

increased CD4-positive, alpha-beta T cell number ( J:176118 )

• in the spleen

increased CD8-positive, alpha-beta T cell number ( J:176118 )

• in the spleen

abnormal B cell physiology ( J:176118 )

• B cells and marginal zone B cells exhibit increased chemotactic response to S1P compared with control cells

• long-term accumulation of B cells in the lymph node is reduced compared with control cells

• marginal zone B cells exhibit decreased chemotactic response to CCL21 compared with control cells

• marginal zone B cells exhibit increased chemotactic response to SEW2871 (S1PR1-selective agonist) compared with control cells

• marginal zone B cell relocalization to the follicle induced by FTY720 treatment is delayed compared to in control mice

• splenic follicular dendritic cells exhibit reduced deposition of phycoerythrin-induced complexes compared with control cells

• however, transfer into a S1P null mouse restores normal lymph node accumulation

hematopoietic system

decreased B cell number ( J:176118 )

• in the lymph nodes

increased B cell number ( J:176118 )

• in the spleen and blood

increased follicular B cell number ( J:176118 )

increased marginal zone B cell number ( J:176118 )

increased CD4-positive, alpha-beta T cell number ( J:176118 )

• in the spleen

increased CD8-positive, alpha-beta T cell number ( J:176118 )

• in the spleen

abnormal B cell physiology ( J:176118 )

• B cells and marginal zone B cells exhibit increased chemotactic response to S1P compared with control cells

• long-term accumulation of B cells in the lymph node is reduced compared with control cells

• marginal zone B cells exhibit decreased chemotactic response to CCL21 compared with control cells

• marginal zone B cells exhibit increased chemotactic response to SEW2871 (S1PR1-selective agonist) compared with control cells

• marginal zone B cell relocalization to the follicle induced by FTY720 treatment is delayed compared to in control mice

• splenic follicular dendritic cells exhibit reduced deposition of phycoerythrin-induced complexes compared with control cells

• however, transfer into a S1P null mouse restores normal lymph node accumulation

Genotype
MGI:5295054

cn3

• Allelic Composition: Grk2^tm1Gwd/Grk2^tm1Mca; Tg(Cd4-cre)1Cwi/0
• Genetic Background: involves: 129 * C57BL/6 * DBA/2

immune system

impaired leukocyte tethering or rolling ( J:176118 )

• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls

• T cells exhibit decreased rolling velocity compared with control cells

increased B cell number ( J:176118 )

• in the spleen

decreased T cell number ( J:176118 )

• in the lymph nodes and blood but not spleen

decreased CD4-positive, alpha-beta T cell number ( J:176118 )

• in the blood and lymph nodes

decreased CD8-positive, alpha-beta T cell number ( J:176118 )

• in the blood and lymph nodes

abnormal T cell physiology ( J:176118 )

• T cells exhibit elevated chemotactic response to S1P and decreased response to CCL21 compared with control cells

• T cells exhibit defective entry into the lymph node compared with control cells

• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls

• T cells exhibit decreased rolling velocity compared with control cells

hematopoietic system

impaired leukocyte tethering or rolling ( J:176118 )

• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls

• T cells exhibit decreased rolling velocity compared with control cells

increased B cell number ( J:176118 )

• in the spleen

decreased T cell number ( J:176118 )

• in the lymph nodes and blood but not spleen

decreased CD4-positive, alpha-beta T cell number ( J:176118 )

• in the blood and lymph nodes

decreased CD8-positive, alpha-beta T cell number ( J:176118 )

• in the blood and lymph nodes

abnormal T cell physiology ( J:176118 )

• T cells exhibit elevated chemotactic response to S1P and decreased response to CCL21 compared with control cells

• T cells exhibit defective entry into the lymph node compared with control cells

• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls

• T cells exhibit decreased rolling velocity compared with control cells

cellular

impaired leukocyte tethering or rolling ( J:176118 )

• lymph node high endothelial venules exhibit a 3- to 4-fold reduction in T cells undergo the rolling-to-sticking transition compared with controls

• T cells exhibit decreased rolling velocity compared with control cells

Genotype
MGI:3763210

cn4

• Allelic Composition: Grk2^tm1Gwd/Grk2^tm1Gwd; Nkx2-5^tm1(cre)Rjs/Nkx2-5⁺
• Genetic Background: involves: 129S4/SvJaeSor * 129S7/SvEvBrd * C57BL/6

mortality/aging

mortality/aging ( J:126501 )

N • unlike in Adrbk1^tm1.1Gwd homozygotes, mice survive into adulthood

homeostasis/metabolism

decreased physiological sensitivity to xenobiotic ( J:126501 )

• inotropic and lusitropic tachyphylaxis effects induced by isoproterenol are blunted

increased physiological sensitivity to xenobiotic ( J:126501 )

• mice exhibit a leftward shift of the peak +dP/dt response to infused doses of isoproterenol with an EC50 of 0.4+/-0.1 ng/g per minute compared to 0.7+/-0.04 ng/g per minute in Adrbk1^tm1Gwd control mice

• when exposed to 30 mg/kg per day isoproterenol, mice develop adverse cardiac remodeling (decreased heart rate, wall thickness to chamber radius ratio) and decreased contractile performance with generalized interstitial and replacement fibrosis in addition to the cardiac dilation and increased left ventricle mass observed in similarly treated Adrbk1^tm1Gwd control mice

cardiovascular system

cardiovascular system phenotype ( J:126501 )

N • unlike in Adrbk1^tm1.1Gwd homozygotes, heart development is normal