Phenotypes associated with this allele

• Allele Symbol: Tgm2^tm1Gml
• Allele Name: targeted mutation 1, Gerry Melino
• Allele ID: MGI:2180638
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Tgm2^tm1Gml/Tgm2^tm1Gml	involves: 129X1/SvJ * C57BL/6	MGI:3029267
hm2	Tgm2^tm1Gml/Tgm2^tm1Gml	involves: C57BL/6	MGI:3803109
hm3	Tgm2^tm1Gml/Tgm2^tm1Gml	involves: C57BL/6 * DBA/1LacJ	MGI:3803114
cx4	Abca1^tm1Jdm/Abca1^tm1Jdm Tgm2^tm1Gml/Tgm2^tm1Gml	involves: C57BL/6 * DBA/1LacJ	MGI:3803113

Genotype
MGI:3029267

hm1

• Allelic Composition: Tgm2^tm1Gml/Tgm2^tm1Gml
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

mortality/aging

increased susceptibility to induced morbidity/mortality ( J:82489 )

• increased death (~60% of treated mice died) after carbon tetrachloride (CCl4) administration

hematopoietic system

decreased erythrocyte cell number ( J:75566 )

• small, but significant

decreased hematocrit ( J:75566 )

• small, but significant

homeostasis/metabolism

hyperglycemia ( J:78633 )

• in fed, but not fasted, state

decreased circulating insulin level ( J:78633 )

• after intraperitoneal glucose administration

impaired glucose tolerance ( J:78633 )

• glucose intolerance after intraperitoneal glucose administration

increased insulin sensitivity ( J:78633 )

• greater hypoglyemic response than controls upon intraperitoneal insulin administration

increased physiological sensitivity to xenobiotic ( J:82489 )

• in those that survived, increased hepatic injury after CCl4 administration

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
maturity-onset diabetes of the young		DOID:0050524	OMIM:606391	J:75566 , J:78633 , J:82489

Genotype
MGI:3803109

hm2

• Allelic Composition: Tgm2^tm1Gml/Tgm2^tm1Gml
• Genetic Background: involves: C57BL/6

mortality/aging

decreased susceptibility to induced morbidity/mortality ( J:131975 )

• after lipopolysaccharide (LPS) treatment to induce acute endotoxic shock, mice show typical signs of endotoxic shock but 90% of treated animals survive to 24 hours compared to 37% of wild-type; all wild-type die by 36 hours whereas no more death of null mice is observed after 36 hours

premature death ( J:126131 )

• mice implanted with B16F1 melanoma tumor cells show reduced survival time after implantation compared to wild-type (<40 days vs >60 days)

cardiovascular system

cardiovascular system phenotype ( J:131975 )

N • in contrast to wild-type mice after 24 hours after LPS treatment, no muscular degradation or myocytolysis is seen

disorganized myocardium ( J:131975 )

• in treated mutants, myocardium is usually preserved, with some animals having mild signs of myofibril disorganization or mitochondrial damage

• most mitochondria do not exhibit shape irregularities, dilation, degeneration of cristae or rupture, compared to those in wild-type myocytes

abnormal cardiovascular system physiology ( J:126414 )

• preischemic values of heart rate (HR), coronary flow (CF), aortic flow (AF) and aortic pressure (AOP) are significantly reduced compared to wild-type values

ventricular fibrillation ( J:126414 )

• incidence of reperfusion-induced ventricular fibrillation is significantly increased (83% vs 33% in wild-type mice)

abnormal response to cardiac infarction ( J:126414 )

• after global ischemia-reperfusion (IR), hearts of Tgm2-null mice show more severe infarct and decreased function compared to wild-type hearts after IR

• after 40 minutes of ischemia followed by 120 minutes of reperfusion, aortic flow is reduced by 3-fold relative to wild-type

increased myocardial infarct size ( J:126414 )

• significantly increased compared to wild-type

cellular

abnormal mitochondrial ATP synthesis coupled electron transport ( J:126414 , J:131975 )

• relative to wild-type, ATP production is impaired in skeletal and cardiac muscle following prolonged physical effort in mice (IR injury) that depletes ATP stores (J:126414)

• when complex III is inhibited by antimycin A, addition of ATP (resulting in ATP hydrolysis and proton pumping by complex V) results in significantly slower rate of membrane polarization than in wild-type mitochondria, reflecting defect in ATPase function (in mice with no IR injury) (J:126414)

• under basal conditions, mitochondrial complex I activity is lower (45% decrease) than in wild-type and complex II activity is significantly increased (by 205%) compared to wild-type (J:131975)

• after LPS-induced septic shock, complex I and II activities are unaffected but in wild-type mitochondria, activities of both complexes are substantially reduced (J:131975)

hematopoietic system

increased macrophage cell number ( J:131975 )

• after LPS treatment, in mutants, there is a 2-fold increase in macrophages infiltrating peritoneal cavity at 24 hours, but in wild-type, infiltrating cells are mixed with neutrophils, mast cells and lymphocytes detected

• 1.5 hours after LPS treatment, serum levels of many cytokines including Il-6, Ifng, and G-CSF are elevated, peaking at 6 hours post-injection; however, while levels remain heightened in wild-type at 24 hours, levels in mutants have returned to steady-state values

• polymorphonuclear neutrophil cell populations are unaffected in contrast to 15-fold increase in neutrophils in peritoneal cavity in wild-type mice at 24 hours

immune system

immune system phenotype ( J:131975 )

N • no significant increase in neutrophil infiltration of venules and glomeruli is detected, compared to 4-fold increase in wild-type relative to baseline after LPS treatment

increased macrophage cell number ( J:131975 )

• after LPS treatment, in mutants, there is a 2-fold increase in macrophages infiltrating peritoneal cavity at 24 hours, but in wild-type, infiltrating cells are mixed with neutrophils, mast cells and lymphocytes detected

• 1.5 hours after LPS treatment, serum levels of many cytokines including Il-6, Ifng, and G-CSF are elevated, peaking at 6 hours post-injection; however, while levels remain heightened in wild-type at 24 hours, levels in mutants have returned to steady-state values

• polymorphonuclear neutrophil cell populations are unaffected in contrast to 15-fold increase in neutrophils in peritoneal cavity in wild-type mice at 24 hours

decreased susceptibility to endotoxin shock ( J:131975 )

renal/urinary system

renal/urinary system phenotype ( J:131975 )

N • 24 hours after LPS treatment, there is no obvious renal damage detected compared to moderate tubular injury observed in wild-type

neoplasm

increased tumor growth/size ( J:126131 )

• after implantation of B16F1 melanoma tumor cells, tumors show signicantly increased growth (larger size) between 16 and 22 days compared to implanted wild-type

homeostasis/metabolism

abnormal response to cardiac infarction ( J:126414 )

• after global ischemia-reperfusion (IR), hearts of Tgm2-null mice show more severe infarct and decreased function compared to wild-type hearts after IR

• after 40 minutes of ischemia followed by 120 minutes of reperfusion, aortic flow is reduced by 3-fold relative to wild-type

increased myocardial infarct size ( J:126414 )

• significantly increased compared to wild-type

muscle

disorganized myocardium ( J:131975 )

• in treated mutants, myocardium is usually preserved, with some animals having mild signs of myofibril disorganization or mitochondrial damage

• most mitochondria do not exhibit shape irregularities, dilation, degeneration of cristae or rupture, compared to those in wild-type myocytes

Genotype
MGI:3803114

hm3

• Allelic Composition: Tgm2^tm1Gml/Tgm2^tm1Gml
• Genetic Background: involves: C57BL/6 * DBA/1LacJ

hematopoietic system

impaired macrophage phagocytosis ( J:132254 )

• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes

abnormal thymus morphology ( J:132254 )

• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type

immune system

impaired macrophage phagocytosis ( J:132254 )

• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes

abnormal thymus morphology ( J:132254 )

• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:132254 )

N • circulating HDL lipoprotein and total cholesterol levels are similar to wild-type

N • circulating triglyceride levels are normal

endocrine/exocrine glands

abnormal thymus morphology ( J:132254 )

• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type

cellular

impaired macrophage phagocytosis ( J:132254 )

• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes

Genotype
MGI:3803113

cx4

• Allelic Composition: Abca1^tm1Jdm/Abca1^tm1Jdm; Tgm2^tm1Gml/Tgm2^tm1Gml
• Genetic Background: involves: C57BL/6 * DBA/1LacJ

mortality/aging

perinatal lethality ( J:132254 )

hematopoietic system

impaired macrophage phagocytosis ( J:132254 )

• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes

• after massive thymic involution induced by dexamethasone treatment, macrophages display reduced phagocytosis ability compared to wild-type, and similar to single-null mice

abnormal thymus morphology ( J:132254 )

• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type, and similar to single null mice

immune system

impaired macrophage phagocytosis ( J:132254 )

• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes

• after massive thymic involution induced by dexamethasone treatment, macrophages display reduced phagocytosis ability compared to wild-type, and similar to single-null mice

abnormal thymus morphology ( J:132254 )

• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type, and similar to single null mice

homeostasis/metabolism

homeostasis/metabolism phenotype ( J:132254 )

N • circulating triglyceride levels are normal in fasting mice

decreased circulating cholesterol level ( J:132254 )

• levels are reduced compared to adult wild-type or Tgm2-null mice

decreased circulating HDL cholesterol level ( J:132254 )

• adult mice show nearly complete loss of HDL cholesterol in fasting mice

endocrine/exocrine glands

abnormal thymus morphology ( J:132254 )

• massive thymic involution induced by dexamethasone treatment results in significant decrease in thymic weight and cellularity compared to wild-type, and similar to single null mice

cellular

impaired macrophage phagocytosis ( J:132254 )

• isolated peritoneal macrophages exposed to apoptotic thymocytes internalize similar numbers of cells (1-2 cells) as wild-type after 15-30 minutes, but this number does not increase with time as with wild-type which internalize 4-5 cells at 60-120 minutes

• after massive thymic involution induced by dexamethasone treatment, macrophages display reduced phagocytosis ability compared to wild-type, and similar to single-null mice