Phenotypes Associated with This Genotype

Genotype
MGI:3850957

• Allelic Composition: Mark2^tm1Hpw/Mark2^tm1Hpw
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:68830 )

• slightly fewer than expected mice are found at 3 weeks

cellular

increased adipocyte glucose uptake ( J:120128 )

• enhanced 4-fold in white adipose tissue and increased in brown adipose tissue

increased mesangial cell number ( J:68830 )

• glomeruli exhibit diffuse mesangial hypercellularity

decreased B cell proliferation ( J:68830 )

• anti-IgM stimulated B cells exhibit a 2- to 3-fold decrease in proliferation compared with wild-type cells

increased B cell proliferation ( J:68830 )

• anti-CD40 treated splenocytes B220+ splenocytes is slightly enhanced compared to similarly treated wild-type cells

reproductive system

decreased litter size ( J:68830 )

• female mice bred with wild-type mice produce smaller than expected litters

immune system

enlarged spleen ( J:68830 )

• in 30% of mice at 7 to 12 months

increased spleen weight ( J:68830 )

• in older mice

spleen hyperplasia ( J:68830 )

• spleen cellularity is increased 2-fold in older mice compared to in wild-type mice

• mice exhibit an expansion of Ter119+HSA+ lymphocytes on the spleen compared with wild-type mice

increased B cell number ( J:68830 )

• young and old mice exhibit lymph node hyperplasia due to an increase in B220+ cells compared to in wild-type mice

abnormal CD4-positive, alpha beta T cell morphology ( J:68830 )

• CD4+ T cells exhibit increased levels of memory markers compared with wild-type cells

abnormal spleen B cell follicle morphology ( J:68830 )

• spleens often exhibit follicular expansion due to enlarged follicular cells compared to in wild-type mice

enlarged lymph nodes ( J:68830 )

• in 30% of mice at 7 to 12 months

lymph node hyperplasia ( J:68830 )

• young and old mice exhibit lymph node hyperplasia due to an increase in B220+ cells compared to in wild-type mice

abnormal immune system physiology ( J:68830 )

• at 5 to 12 months, 85% of mice exhibit some immunological disorders unlike wild-type mice

decreased B cell proliferation ( J:68830 )

• anti-IgM stimulated B cells exhibit a 2- to 3-fold decrease in proliferation compared with wild-type cells

increased B cell proliferation ( J:68830 )

• anti-CD40 treated splenocytes B220+ splenocytes is slightly enhanced compared to similarly treated wild-type cells

salivary gland inflammation ( J:68830 )

• parietal salivary glands exhibit lymphocytic infiltrates unlike in wild-type mice

abnormal humoral immune response ( J:68830 )

• T-cell-dependent IgG1 and IgG2a response to NP-KLH are 7.5-fold and 9.5-fold, respectively, compared with wild-type mice

decreased IgG3 level ( J:68830 )

• 17 days after treatment with NP-Ficoll, mice exhibit 3.5-fold lower serum IgG3 levels compared with similarly treated wild-type mice

decreased IgM level ( J:68830 )

• 17 days after treatment with NP-Ficoll, mice exhibit 4-fold lower IgM serum levels compared with similarly treated wild-type mice

increased interferon-gamma secretion ( J:68830 )

• concanavalin A or ati-CD3 antibody treated splenocytes produce 3-fold more IFN-gamma compared with similarly treated wild-type mice

• Th1 cells produce 3-fold more IFN-gamma than wild-type cells

• following TCR cross-linking, T cells produce more IFN-gamma than similarly treated wild-type cells

increased interleukin-4 secretion ( J:68830 )

• Th2 cells produce 3-fold more IL4 than wild-type cells

• following TCR cross-linking, T cells produce more IL4 than similarly treated wild-type cells

kidney inflammation ( J:68830 )

• kidneys exhibit lymphocytic infiltrates unlike in wild-type mice

glomerulonephritis ( J:68830 )

• mice exhibit membranoproliferative glomerulonephritis

lung inflammation ( J:68830 )

• lungs exhibit lymphocytic infiltrates unlike in wild-type mice

homeostasis/metabolism

decreased circulating insulin-like growth factor I level ( J:120128 )

• 25% at 7 weeks

decreased circulating leptin level ( J:120128 )

• 5-fold when mice are fed a high-fat diet

decreased circulating cholesterol level ( J:120128 )

• when mice are fed a high-fat diet

decreased circulating triglyceride level ( J:120128 )

• when mice are fed a high-fat diet

increased energy expenditure ( J:120128 )

• 27% when fed a high fat diet

decreased susceptibility to diet-induced obesity ( J:120128 )

• in male mice

abnormal glucose homeostasis ( J:120128 )

• insulin-stimulated glucose infusion rate and turnover are increased compared to in wild-type mice

hypoglycemia ( J:120128 )

• mildly under fed conditions

decreased circulating insulin level ( J:120128 )

• 5-fold when mice are fed a high-fat diet and also decreased when mice are fed normal chow

improved glucose tolerance ( J:120128 )

increased insulin sensitivity ( J:120128 )

• enhanced 35%

decreased circulating adiponectin level ( J:163905 )

• in females

increased urine protein level ( J:68830 )

• mild to severe in 29% of males and 17% of females

hemoglobinuria ( J:68830 )

• in 33% of males and 45% of females

increased basal metabolism ( J:120128 )

• 7% when fed a high fat diet

renal/urinary system

abnormal glomerular capillary morphology ( J:68830 )

• thickening of the capillary walls

increased mesangial cell number ( J:68830 )

• glomeruli exhibit diffuse mesangial hypercellularity

increased urine protein level ( J:68830 )

• mild to severe in 29% of males and 17% of females

hemoglobinuria ( J:68830 )

• in 33% of males and 45% of females

kidney inflammation ( J:68830 )

• kidneys exhibit lymphocytic infiltrates unlike in wild-type mice

glomerulonephritis ( J:68830 )

• mice exhibit membranoproliferative glomerulonephritis

increased renal glomerulus lobularity ( J:68830 )

• glomeruli are hypercellular and lobulated unlike in wild-type mice

adipose tissue

decreased brown adipose tissue amount ( J:120128 , J:163905 )

• BAT mass is reduced even when mice are fed a high-fat diet (J:163905)

decreased white adipose tissue amount ( J:120128 , J:163905 )

• in the epididymal fat pads at 12 weeks (J:120128)

• WAT mass is reduced even when mice are fed a high-fat diet (J:163905)

decreased percent body fat/body weight ( J:120128 )

• 14% compared to 23% in wild-type mice

increased adipocyte glucose uptake ( J:120128 )

• enhanced 4-fold in white adipose tissue and increased in brown adipose tissue

digestive/alimentary system

rectal prolapse ( J:68830 )

• 30% of mice exhibit colorectal prolapse

• 41% of aged females and 18% of aged males exhibit colorectal prolapse

salivary gland inflammation ( J:68830 )

• parietal salivary glands exhibit lymphocytic infiltrates unlike in wild-type mice

growth/size/body

decreased embryo weight ( J:120128 )

• by 20% at E13.5

decreased body weight ( J:68830 , J:120128 )

• 25% to 30% (J:68830)

• 20% (J:120128)

decreased body length ( J:120128 )

• 8%

decreased susceptibility to weight gain ( J:163905 )

• after 7 weeks on a high-fat diet, mice do not gain weight

decreased susceptibility to diet-induced obesity ( J:120128 )

• in male mice

postnatal growth retardation ( J:68830 )

enlarged spleen ( J:68830 )

• in 30% of mice at 7 to 12 months

increased spleen weight ( J:68830 )

• in older mice

spleen hyperplasia ( J:68830 )

• spleen cellularity is increased 2-fold in older mice compared to in wild-type mice

• mice exhibit an expansion of Ter119+HSA+ lymphocytes on the spleen compared with wild-type mice

endocrine/exocrine glands

salivary gland inflammation ( J:68830 )

• parietal salivary glands exhibit lymphocytic infiltrates unlike in wild-type mice

respiratory system

lung inflammation ( J:68830 )

• lungs exhibit lymphocytic infiltrates unlike in wild-type mice

hematopoietic system

decreased B cell proliferation ( J:68830 )

• anti-IgM stimulated B cells exhibit a 2- to 3-fold decrease in proliferation compared with wild-type cells

increased B cell proliferation ( J:68830 )

• anti-CD40 treated splenocytes B220+ splenocytes is slightly enhanced compared to similarly treated wild-type cells

enlarged spleen ( J:68830 )

• in 30% of mice at 7 to 12 months

increased spleen weight ( J:68830 )

• in older mice

spleen hyperplasia ( J:68830 )

• spleen cellularity is increased 2-fold in older mice compared to in wild-type mice

• mice exhibit an expansion of Ter119+HSA+ lymphocytes on the spleen compared with wild-type mice

increased B cell number ( J:68830 )

• young and old mice exhibit lymph node hyperplasia due to an increase in B220+ cells compared to in wild-type mice

abnormal CD4-positive, alpha beta T cell morphology ( J:68830 )

• CD4+ T cells exhibit increased levels of memory markers compared with wild-type cells

abnormal spleen B cell follicle morphology ( J:68830 )

• spleens often exhibit follicular expansion due to enlarged follicular cells compared to in wild-type mice

decreased IgG3 level ( J:68830 )

• 17 days after treatment with NP-Ficoll, mice exhibit 3.5-fold lower serum IgG3 levels compared with similarly treated wild-type mice

decreased IgM level ( J:68830 )

• 17 days after treatment with NP-Ficoll, mice exhibit 4-fold lower IgM serum levels compared with similarly treated wild-type mice

behavior/neurological

abnormal eating behavior ( J:120128 )

• 2-fold when fed a high fat diet

embryo

decreased embryo weight ( J:120128 )

• by 20% at E13.5

liver/biliary system

decreased susceptibility to age-related hepatic steatosis ( J:120128 )

• resistance to the onset of hepatic steatosis in aged mice fed normal chow

cardiovascular system

abnormal glomerular capillary morphology ( J:68830 )

• thickening of the capillary walls