Phenotypes associated with this allele

• Allele Symbol: Lat2^tm1Wz
• Allele Name: targeted mutation 1, Weiguo Zhang
• Allele ID: MGI:3510962
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Lat2^tm1Wz/Lat2^tm1Wz	B6.Cg-Lat2^tm1Wz	MGI:3695386
hm2	Lat2^tm1Wz/Lat2^tm1Wz	involves: C57BL/6	MGI:3511019
hm3	Lat2^tm1Wz/Lat2^tm1Wz	Not Specified	MGI:5316283
cx4	Lat^tm1.1Lov/Lat^tm1.1Lov Lat2^tm1Wz/Lat2^tm1Wz	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3695389
cx5	Lat^tm1Les/Lat^tm1Les Lat2^tm1Wz/Lat2^tm1Wz	involves: C57BL/6	MGI:3511020

Genotype
MGI:3695386

hm1

• Allelic Composition: Lat2^tm1Wz/Lat2^tm1Wz
• Genetic Background: B6.Cg-Lat2^tm1Wz

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

immune system

spleen hyperplasia ( J:116157 )

• enlarged in mice older than 6 months of age but not in mice at 5 - 8 weeks of age

• total number of splenocytes is increased to (9.5 +/- 2.0) x 10⁷ compared to (4.4 +/- 0.6) x 10⁷ in wild-type mice

abnormal T cell physiology ( J:116157 )

• increased expression of CD25, CD69, and CD44 and decreased expression of CD62L and CD45RB

increased T cell proliferation ( J:116157 )

• increased in the presence of low concentrations of anti-CD3 (0.05 mg/ul) compared to wild-type mice

abnormal CD8-positive, alpha-beta T cell physiology ( J:116157 )

• isolated cells produce more IL-2, IL-10, TNFA, and IFNG after stimulation with PMA and ionomycin

abnormal cytokine secretion ( J:116157 )

• splenocytes stimulated with PMA and ionomycin produce more IL-2, IL10, and IFNG

increased autoantibody level ( J:116157 )

• elevated at 6 months of age and even more so at 1 year

increased anti-double stranded DNA antibody level ( J:116157 )

• high titers of dsDNA antibodies are found at 6 months of age

hematopoietic system

spleen hyperplasia ( J:116157 )

• enlarged in mice older than 6 months of age but not in mice at 5 - 8 weeks of age

• total number of splenocytes is increased to (9.5 +/- 2.0) x 10⁷ compared to (4.4 +/- 0.6) x 10⁷ in wild-type mice

abnormal T cell physiology ( J:116157 )

• increased expression of CD25, CD69, and CD44 and decreased expression of CD62L and CD45RB

increased T cell proliferation ( J:116157 )

• increased in the presence of low concentrations of anti-CD3 (0.05 mg/ul) compared to wild-type mice

abnormal CD8-positive, alpha-beta T cell physiology ( J:116157 )

• isolated cells produce more IL-2, IL-10, TNFA, and IFNG after stimulation with PMA and ionomycin

cellular

increased T cell proliferation ( J:116157 )

• increased in the presence of low concentrations of anti-CD3 (0.05 mg/ul) compared to wild-type mice

growth/size/body

spleen hyperplasia ( J:116157 )

• enlarged in mice older than 6 months of age but not in mice at 5 - 8 weeks of age

• total number of splenocytes is increased to (9.5 +/- 2.0) x 10⁷ compared to (4.4 +/- 0.6) x 10⁷ in wild-type mice

Genotype
MGI:3511019

hm2

• Allelic Composition: Lat2^tm1Wz/Lat2^tm1Wz
• Genetic Background: involves: C57BL/6

immune system

abnormal mast cell physiology ( J:93951 )

• antigen-stimulated granule release is significantly enhanced compared to wild-type

• T, B, dendritic, and natural killer cell development are all normal

hematopoietic system

abnormal mast cell physiology ( J:93951 )

• antigen-stimulated granule release is significantly enhanced compared to wild-type

• T, B, dendritic, and natural killer cell development are all normal

Genotype
MGI:5316283

hm3

• Allelic Composition: Lat2^tm1Wz/Lat2^tm1Wz
• Genetic Background: Not Specified

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:181866 )

• following LPS-induced septic shock

immune system

increased mast cell degranulation ( J:181866 )

• mediated by Fc RI with increased calcium flux

abnormal T cell physiology ( J:181866 )

• T cells stimulated with anti-CD3 in the presence of IL2, rested and re-stimulated with anti-CD3 and anti-CD8 exhibit enhanced calcium flux compared with similarly treated wild-type cells

increased circulating interleukin-6 level ( J:181866 )

• following LPS-induced septic shock

increased circulating tumor necrosis factor level ( J:181866 )

• following LPS-induced septic shock

increased interferon-gamma secretion ( J:181866 )

• from CD8+ T cells stimulated with anti-CD3 in the presence of IL2, rested and re-stimulated with anti-CD3 and anti-CD8

increased interleukin-10 secretion ( J:181866 )

• in LPS-treated bone marrow-derived dendritic cells

• following LPS-induced septic shock

decreased interleukin-12 secretion ( J:181866 )

• in LPS-treated bone marrow-derived dendritic cells

increased susceptibility to endotoxin shock ( J:181866 )

• mice are hyperresponsive to LPS-induced septic shock with increased serum levels of TNF, IL6, and IL10, and die within 30 hours compared with wild-type mice

• however, IL12 serum levels are normal

homeostasis/metabolism

increased circulating interleukin-6 level ( J:181866 )

• following LPS-induced septic shock

increased circulating tumor necrosis factor level ( J:181866 )

• following LPS-induced septic shock

increased susceptibility to xenobiotic induced morbidity/mortality ( J:181866 )

• following LPS-induced septic shock

hematopoietic system

increased mast cell degranulation ( J:181866 )

• mediated by Fc RI with increased calcium flux

abnormal T cell physiology ( J:181866 )

• T cells stimulated with anti-CD3 in the presence of IL2, rested and re-stimulated with anti-CD3 and anti-CD8 exhibit enhanced calcium flux compared with similarly treated wild-type cells

cellular

increased mast cell degranulation ( J:181866 )

• mediated by Fc RI with increased calcium flux

Genotype
MGI:3695389

cx4

• Allelic Composition: Lat^tm1.1Lov/Lat^tm1.1Lov; Lat2^tm1Wz/Lat2^tm1Wz
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

immune system

enlarged spleen ( J:116157 )

• enlarged at 11 weeks of age

• spleen size is increased compared to Lat single homozygotes

spleen hyperplasia ( J:116157 )

• toal splenocyte number is (3.6 +/- 0.2) x 10⁸ compared to (2.0 +/- 0.2) x 10⁸ in Lat single homozygotes and (2.7 +/- 0.2) x 10⁷ in wild-type mice

abnormal CD4-positive, alpha beta T cell morphology ( J:116157 )

• about 68% of splenocytes are CD4+ cells

enlarged lymph nodes ( J:116157 )

• enlarged at 11 weeks of age

• lymph node size is increased compared to Lat single homozygotes

increased anti-double stranded DNA antibody level ( J:116157 )

• high titers of dsDNA antibodies are present at 6 weeks of age

• titers of dsDNA antibodies are higher and detected earlier than in Lat single homozygotes

hematopoietic system

enlarged spleen ( J:116157 )

• enlarged at 11 weeks of age

• spleen size is increased compared to Lat single homozygotes

spleen hyperplasia ( J:116157 )

• toal splenocyte number is (3.6 +/- 0.2) x 10⁸ compared to (2.0 +/- 0.2) x 10⁸ in Lat single homozygotes and (2.7 +/- 0.2) x 10⁷ in wild-type mice

abnormal CD4-positive, alpha beta T cell morphology ( J:116157 )

• about 68% of splenocytes are CD4+ cells

growth/size/body

enlarged spleen ( J:116157 )

• enlarged at 11 weeks of age

• spleen size is increased compared to Lat single homozygotes

spleen hyperplasia ( J:116157 )

• toal splenocyte number is (3.6 +/- 0.2) x 10⁸ compared to (2.0 +/- 0.2) x 10⁸ in Lat single homozygotes and (2.7 +/- 0.2) x 10⁷ in wild-type mice

Genotype
MGI:3511020

cx5

• Allelic Composition: Lat^tm1Les/Lat^tm1Les; Lat2^tm1Wz/Lat2^tm1Wz
• Genetic Background: involves: C57BL/6

immune system

abnormal mast cell physiology ( J:93951 )

• granules are not released following antigen stimulation similar to Lat^tm1Les homozygotes

hematopoietic system

abnormal mast cell physiology ( J:93951 )

• granules are not released following antigen stimulation similar to Lat^tm1Les homozygotes