Phenotypes associated with this allele

• Allele Symbol: Tg(Lck-Tnfsf14)24Yxf
• Allele Name: transgene insertion 24, Yang-Xin Fu
• Allele ID: MGI:3849832
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Ltbr^tm1Kpf/Ltbr^tm1Kpf Tg(Lck-Tnfsf14)24Yxf/?	B6.Cg-Ltbr^tm1Kpf Tg(Lck-Tnfsf14)24Yxf	MGI:3849890
cx2	Tg(Lck-Tnfsf14)24Yxf/? Tnfrsf14^tm1Kpf/Tnfrsf14^tm1Kpf	involves: 129P2/OlaHsd * C57BL/6	MGI:3849889
tg3	Tg(Lck-Tnfsf14)24Yxf/?	C57BL/6-Tg(Lck-Tnfsf14)24Yxf	MGI:3849839

Genotype
MGI:3849890

cx1

• Allelic Composition: Ltbr^tm1Kpf/Ltbr^tm1Kpf; Tg(Lck-Tnfsf14)24Yxf/?
• Genetic Background: B6.Cg-Ltbr^tm1Kpf Tg(Lck-Tnfsf14)24Yxf

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

digestive/alimentary system

digestive/alimentary phenotype ( J:128976 )

N • mice show no abnormality in the intestine and no significant T cell-mediated inflammation in the gut

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:120962 )

N • the high serum cholesterol levels characteristic of the transgenic mice does not occur in these mice

immune system

immune system phenotype ( J:128976 )

N • serum IgA levels are normal and mice show no significant T cell-mediated inflammation in the gut

Genotype
MGI:3849889

cx2

• Allelic Composition: Tg(Lck-Tnfsf14)24Yxf/?; Tnfrsf14^tm1Kpf/Tnfrsf14^tm1Kpf
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6

homeostasis/metabolism

increased circulating cholesterol level ( J:120962 )

• the high serum cholesterol levels characteristic of the transgenic mice is exacerbated on the null background

Genotype
MGI:3849839

tg3

• Allelic Composition: Tg(Lck-Tnfsf14)24Yxf/?
• Genetic Background: C57BL/6-Tg(Lck-Tnfsf14)24Yxf

digestive/alimentary system

increased enterocyte apoptosis ( J:128976 )

• increase in apoptosis of gut epithelial cells

abnormal intestine morphology ( J:128976 )

• intestinal wall is diffusely thickened

abnormal intestinal epithelium morphology ( J:128976 )

• epithelial cell damage in the intestine is associated with intraepithelial neutrophils, lymphocytes, and occasional crypt abscesses

intestinal inflammation ( J:128976 )

• mice exhibit a patchy interstitial infiltrate without interstitial fibrosis indicating focal interstitial inflammation

• intestine shows an increase in the number of IgA+ plasma cells that massively infiltrate the lamina propria, with many lymphoid follicle-like structures infiltrating the lamina propria of the colon

• mice develop intestinal inflammation with increased lamina propria neutrophils, lymphocytes, plasma cells, and focal epithelial damage

• many of the lamina propria leukocytes are T cells and granulocytes

colitis ( J:129951 )

• at 5-8 months of age, mice develop a colitis like disease with a diffuse thickening of the intestinal wall, inflammatory cell infiltrate in the lamina propria and submucosa, and prominent germinal center formation in a diffuse pattern

small intestinal inflammation ( J:120962 )

• the small intestine is inflamed in 6 month old mice

cellular

increased enterocyte apoptosis ( J:128976 )

• increase in apoptosis of gut epithelial cells

increased T cell proliferation ( J:129951 )

• T cells isolated from mice are in a hyper-proliferative state with blastogenic qualities

• there is more than a three fold expansion in the percentage of T cells expressing CD62L^lowCD44^high activation markers

hematopoietic system

increased spleen weight ( J:129951 )

• splenomegaly is evident at 5-8 months of age

• mean weight of spleen is 339.6 mg compared to 88.5 mg in wild-type mice

spleen hyperplasia ( J:129951 )

• the number of splenocytes is about double that of control

extramedullary hematopoiesis ( J:129951 )

• hematopoiesis of the granulocyte / macrophage lineage is detected in the spleen

increased IgA level ( J:128976 )

• serum IgA levels are elevated up to 30- to 40-fold by 6-8 months of age

• serm IgA levels are 10-fold higher as early as 7 weeks of age, before intestinal inflammation is identifiable

• mice exhibit increased glomeruli mesangial deposition of IgA

• serum predominantly contains polymeric IgA rather than monomeric IgA

increased IgG level ( J:128976 )

• mice show IgG deposition in the glomeruli

abnormal T cell physiology ( J:120962 , J:129951 )

• T cells disrupt lipid homeostasis in these mice as evidenced by the hypertriglyceridemia and hypercholesterolemia (J:120962)

• transgenic T cells transferred into wild-type hosts cause rises in serum cholesterol (J:120962)

• transgenic T cells also cause a rise in cholesterol levels when transferred into LDLR^tm1Her null mice (J:120962)

• there is a five-fold increase in the number of T cells secreting IFN-gamma after in vitro activation (J:129951)

• there is also an increase in the number of T cells producing IL-4 (J:129951)

• there is a three-fold increase in GM-CSF production by splenocytes (J:129951)

increased T cell proliferation ( J:129951 )

• T cells isolated from mice are in a hyper-proliferative state with blastogenic qualities

• there is more than a three fold expansion in the percentage of T cells expressing CD62L^lowCD44^high activation markers

immune system

increased spleen weight ( J:129951 )

• splenomegaly is evident at 5-8 months of age

• mean weight of spleen is 339.6 mg compared to 88.5 mg in wild-type mice

spleen hyperplasia ( J:129951 )

• the number of splenocytes is about double that of control

increased IgA level ( J:128976 )

• serum IgA levels are elevated up to 30- to 40-fold by 6-8 months of age

• serm IgA levels are 10-fold higher as early as 7 weeks of age, before intestinal inflammation is identifiable

• mice exhibit increased glomeruli mesangial deposition of IgA

• serum predominantly contains polymeric IgA rather than monomeric IgA

increased IgG level ( J:128976 )

• mice show IgG deposition in the glomeruli

abnormal T cell physiology ( J:120962 , J:129951 )

• T cells disrupt lipid homeostasis in these mice as evidenced by the hypertriglyceridemia and hypercholesterolemia (J:120962)

• transgenic T cells transferred into wild-type hosts cause rises in serum cholesterol (J:120962)

• transgenic T cells also cause a rise in cholesterol levels when transferred into LDLR^tm1Her null mice (J:120962)

• there is a five-fold increase in the number of T cells secreting IFN-gamma after in vitro activation (J:129951)

• there is also an increase in the number of T cells producing IL-4 (J:129951)

• there is a three-fold increase in GM-CSF production by splenocytes (J:129951)

increased T cell proliferation ( J:129951 )

• T cells isolated from mice are in a hyper-proliferative state with blastogenic qualities

• there is more than a three fold expansion in the percentage of T cells expressing CD62L^lowCD44^high activation markers

abnormal complement protein level ( J:128976 )

• mice exhibit increased glomerular deposition of complement C3

abnormal lymph node cell ratio ( J:129951 )

• ratio of T cells to B cells is almost 5-fold greater than in controls

lymph node hyperplasia ( J:129951 )

• lymph nodes are larger by 5-8 months of age

• there is a 7-fold increase in the number of lymph node cells

• the increase in cell number is due expansion of the T cell zone

increased autoantibody level ( J:129951 )

• rheumatoid factors are increased in these mice

increased anti-nuclear antigen antibody level ( J:128976 )

• presence of anti-DNA IgA antibody in aged mice

increased anti-double stranded DNA antibody level ( J:129951 )

• anti-DNA antibody levels are eight-fold higher than controls

abnormal inflammatory response ( J:128976 )

• IgA level in fecal extracts of aged mice is decreased indicating reduced IgA secretion

• transgenic mice administered a labeled polymeric IgA intravenously show a higher level of polymeric IgA in serum compared to wild-type mice indicating a longer half-life and that mice have defects in clearing the polymeric IgA from the circulation

intestinal inflammation ( J:128976 )

• mice exhibit a patchy interstitial infiltrate without interstitial fibrosis indicating focal interstitial inflammation

• intestine shows an increase in the number of IgA+ plasma cells that massively infiltrate the lamina propria, with many lymphoid follicle-like structures infiltrating the lamina propria of the colon

• mice develop intestinal inflammation with increased lamina propria neutrophils, lymphocytes, plasma cells, and focal epithelial damage

• many of the lamina propria leukocytes are T cells and granulocytes

colitis ( J:129951 )

• at 5-8 months of age, mice develop a colitis like disease with a diffuse thickening of the intestinal wall, inflammatory cell infiltrate in the lamina propria and submucosa, and prominent germinal center formation in a diffuse pattern

small intestinal inflammation ( J:120962 )

• the small intestine is inflamed in 6 month old mice

liver inflammation ( J:129951 )

• inflammatory infiltrate in the portal areas of the liver are observed

myositis ( J:129951 )

• inflammatory infiltrate in skeletal muscle is observed

glomerulonephritis ( J:129951 )

• mice spontaneously develop diffuse global proliferative glomerulonephritis involving over 80% of the glomeruli

• the involved glomeruli are diffusely enlarged, demonstrating mesangial prominence and intracapillary and extracapillary proliferation with obliteration of the capillary lumina

• basement membranes are thickened

lung inflammation ( J:129951 )

• inflammatory infiltrate in the pulmonary interstitial is observed

liver/biliary system

liver inflammation ( J:129951 )

• inflammatory infiltrate in the portal areas of the liver are observed

abnormal liver morphology ( J:120962 )

• at 4 to 8 weeks of age, T cell numbers are increased in the liver without any signs of inflammation

muscle

myositis ( J:129951 )

• inflammatory infiltrate in skeletal muscle is observed

respiratory system

lung inflammation ( J:129951 )

• inflammatory infiltrate in the pulmonary interstitial is observed

homeostasis/metabolism

increased circulating cholesterol level ( J:120962 )

• cholesterol levels are almost double those of control as 4 to 8 weeks of age

• cholesterol levels are more than double those controls when mice are fed a high-fat diet

increased circulating triglyceride level ( J:120962 )

• circulating triglyceride levels are elevated by 4 to 8 weeks of age

• this hypertriglyceridemia is elevated further when mice are fed a high-fat diet

abnormal complement protein level ( J:128976 )

• mice exhibit increased glomerular deposition of complement C3

increased urine protein level ( J:128976 )

• aged mice exhibit proteinuria

hematuria ( J:128976 )

• aged mice exhibit spontaneous microscopic hematuria

integument

spontaneous skin ulceration ( J:129951 )

• plaque-like cutaneous lesions ranging from 0.3 cm to 2 cm along with ulceration and scar formation occur in virtually all mice by 5 months of age

renal/urinary system

increased urine protein level ( J:128976 )

• aged mice exhibit proteinuria

hematuria ( J:128976 )

• aged mice exhibit spontaneous microscopic hematuria

abnormal renal glomerulus morphology ( J:128976 )

• mice exhibit increased glomerular deposition of IgA and complement C3

• mice show IgG and weak IgM deposition in the glomeruli

glomerulonephritis ( J:129951 )

• mice spontaneously develop diffuse global proliferative glomerulonephritis involving over 80% of the glomeruli

• the involved glomeruli are diffusely enlarged, demonstrating mesangial prominence and intracapillary and extracapillary proliferation with obliteration of the capillary lumina

• basement membranes are thickened

abnormal glomerular mesangium morphology ( J:128976 )

• kidney shows a wide acellular mesangium filled with a periodic acid-Schiff+ material

glomerulosclerosis ( J:128976 )

• glomeruli are almost entirely sclerotic in some mice

renal glomerular immunoglobulin deposits ( J:129951 )

• Ig deposits are visible in a coarsely-granular manner

growth/size/body

increased spleen weight ( J:129951 )

• splenomegaly is evident at 5-8 months of age

• mean weight of spleen is 339.6 mg compared to 88.5 mg in wild-type mice

spleen hyperplasia ( J:129951 )

• the number of splenocytes is about double that of control

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
IgA glomerulonephritis		DOID:2986	OMIM:161950	J:128976