Phenotypes associated with this allele

• Allele Symbol: Cbl^tm2Wlan
• Allele Name: targeted mutation 2, Wallace Y Langdon
• Allele ID: MGI:3610727
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cbl^tm2Wlan/Cbl^tm2Wlan	involves: 129X1/SvJ * C57BL/6	MGI:3623284
ht2	Cbl^tm1Ddlb/Cbl^tm2Wlan	involves: 129S1/Sv * 129X1/SvJ * C57BL/6	MGI:3623285
ht3	Cbl^tm1Ddlb/Cbl^tm2Wlan	involves: 129S1/Sv * C57BL/6	MGI:3711320

Genotype
MGI:3623284

hm1

• Allelic Composition: Cbl^tm2Wlan/Cbl^tm2Wlan
• Genetic Background: involves: 129X1/SvJ * C57BL/6

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

mortality/aging

lethality throughout fetal growth and development, incomplete penetrance ( J:103366 )

• by E19 only 4% of embryos are homozygous compared to 22% at E14

neonatal lethality, incomplete penetrance ( J:103366 )

• about 25% of live born homozygotes die within 24 hours

immune system

abnormal thymus morphology ( J:103366 )

abnormal thymus size ( J:103366 )

• progressive loss of the thymus as mice age beginning at 2 weeks of age

thymus hypoplasia ( J:103366 )

• by 40 weeks of age mice have less than 1% of the number of thymocytes seen in heterozygous controls

abnormal spleen morphology ( J:103366 )

enlarged spleen ( J:103366 )

• spleen is enlarged about 2.5- to 3.5-fold compared to wild-type mice due to expansion of the red pulp

spleen hyperplasia ( J:103366 )

• increase in the number of megakaryocytes, megakaryoblasts, and myelocytes but no increase in the number of lymphocytes is seen in the spleen

increased spleen red pulp amount ( J:103366 )

• expanded

pigmentation

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

darkened coat color ( J:103366 )

• darker coat compared to both agouti and black wild-type mice

abnormal foot pigmentation ( J:103366 )

• darker feet compared to both agouti and black wild-type mice

increased tail pigmentation ( J:103366 )

• darker tails compared to both agouti and black wild-type mice

limbs/digits/tail

increased tail pigmentation ( J:103366 )

• darker tails compared to both agouti and black wild-type mice

hematopoietic system

abnormal thymus morphology ( J:103366 )

abnormal thymus size ( J:103366 )

• progressive loss of the thymus as mice age beginning at 2 weeks of age

thymus hypoplasia ( J:103366 )

• by 40 weeks of age mice have less than 1% of the number of thymocytes seen in heterozygous controls

abnormal spleen morphology ( J:103366 )

enlarged spleen ( J:103366 )

• spleen is enlarged about 2.5- to 3.5-fold compared to wild-type mice due to expansion of the red pulp

spleen hyperplasia ( J:103366 )

• increase in the number of megakaryocytes, megakaryoblasts, and myelocytes but no increase in the number of lymphocytes is seen in the spleen

increased spleen red pulp amount ( J:103366 )

• expanded

hearing/vestibular/ear

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

craniofacial

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

integument

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

darkened coat color ( J:103366 )

• darker coat compared to both agouti and black wild-type mice

abnormal foot pigmentation ( J:103366 )

• darker feet compared to both agouti and black wild-type mice

increased tail pigmentation ( J:103366 )

• darker tails compared to both agouti and black wild-type mice

endocrine/exocrine glands

abnormal thymus morphology ( J:103366 )

abnormal thymus size ( J:103366 )

• progressive loss of the thymus as mice age beginning at 2 weeks of age

thymus hypoplasia ( J:103366 )

• by 40 weeks of age mice have less than 1% of the number of thymocytes seen in heterozygous controls

growth/size/body

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

enlarged spleen ( J:103366 )

• spleen is enlarged about 2.5- to 3.5-fold compared to wild-type mice due to expansion of the red pulp

spleen hyperplasia ( J:103366 )

• increase in the number of megakaryocytes, megakaryoblasts, and myelocytes but no increase in the number of lymphocytes is seen in the spleen

Genotype
MGI:3623285

ht2

• Allelic Composition: Cbl^tm1Ddlb/Cbl^tm2Wlan
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6

mortality/aging

prenatal lethality, incomplete penetrance ( J:103366 )

• fewer than expected mutant mice are found at birth (31.8% rather than the expected 50%) however neonatal mortality is similar to mice heterozygous for Cbl^tm1Ddlb alone

immune system

abnormal thymus morphology ( J:103366 )

abnormal thymus size ( J:103366 )

• progressive loss of the thymus as mice age beginning at 2 weeks of age

thymus hypoplasia ( J:103366 )

• by 40 weeks of age mice have less than 1% of the number of thymocytes seen in heterozygous controls

abnormal T cell differentiation ( J:103366 )

abnormal double-negative T cell morphology ( J:103366 )

• slight but significant increase in the proportion of double negative T cells

decreased single-positive T cell number ( J:103366 )

• about a 40% decrease in the proportion of single positive T cells

abnormal spleen morphology ( J:103366 )

enlarged spleen ( J:103366 )

• spleen is enlarged about 2.5- to 3.5-fold compared to wild-type mice due to expansion of the red pulp

spleen hyperplasia ( J:103366 )

• increase in the number of megakaryocytes, megakaryoblasts, and myelocytes but no increase in the number of lymphocytes is seen in the spleen

increased spleen red pulp amount ( J:103366 )

• expanded

abnormal splenic cell ratio ( J:103366 )

• the proportion of splenic T cells is reduced by about 80% compared to control littermates

abnormal T cell physiology ( J:103366 )

• cultured thymocytes are more sensitive to apoptosis induced by anti-CD3 antibodies alone

abnormal T cell activation ( J:103366 )

• a greater proportion of CD4+ T cells express higher levels of activation markers (CD44 and CD25) but the absolute numbers of these cells are decreased compared to mice heterozygous or homozygous for Cbl^tm1Ddlb alone

abnormal lymph node cell ratio ( J:103366 )

• lymph nodes contain 50% fewer CD4+ and CD8+ T cells and an increased proportion of B cells

pigmentation

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

darkened coat color ( J:103366 )

• darker coat compared to both agouti and black wild-type mice

abnormal foot pigmentation ( J:103366 )

• darker feet compared to both agouti and black wild-type mice

increased tail pigmentation ( J:103366 )

• darker tails compared to both agouti and black wild-type mice

hematopoietic system

abnormal thymus morphology ( J:103366 )

abnormal thymus size ( J:103366 )

• progressive loss of the thymus as mice age beginning at 2 weeks of age

thymus hypoplasia ( J:103366 )

• by 40 weeks of age mice have less than 1% of the number of thymocytes seen in heterozygous controls

abnormal T cell differentiation ( J:103366 )

abnormal double-negative T cell morphology ( J:103366 )

• slight but significant increase in the proportion of double negative T cells

decreased single-positive T cell number ( J:103366 )

• about a 40% decrease in the proportion of single positive T cells

abnormal spleen morphology ( J:103366 )

enlarged spleen ( J:103366 )

• spleen is enlarged about 2.5- to 3.5-fold compared to wild-type mice due to expansion of the red pulp

spleen hyperplasia ( J:103366 )

• increase in the number of megakaryocytes, megakaryoblasts, and myelocytes but no increase in the number of lymphocytes is seen in the spleen

increased spleen red pulp amount ( J:103366 )

• expanded

abnormal splenic cell ratio ( J:103366 )

• the proportion of splenic T cells is reduced by about 80% compared to control littermates

abnormal T cell physiology ( J:103366 )

• cultured thymocytes are more sensitive to apoptosis induced by anti-CD3 antibodies alone

abnormal T cell activation ( J:103366 )

• a greater proportion of CD4+ T cells express higher levels of activation markers (CD44 and CD25) but the absolute numbers of these cells are decreased compared to mice heterozygous or homozygous for Cbl^tm1Ddlb alone

hearing/vestibular/ear

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

craniofacial

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

integument

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

darkened coat color ( J:103366 )

• darker coat compared to both agouti and black wild-type mice

abnormal foot pigmentation ( J:103366 )

• darker feet compared to both agouti and black wild-type mice

increased tail pigmentation ( J:103366 )

• darker tails compared to both agouti and black wild-type mice

limbs/digits/tail

increased tail pigmentation ( J:103366 )

• darker tails compared to both agouti and black wild-type mice

endocrine/exocrine glands

abnormal thymus morphology ( J:103366 )

abnormal thymus size ( J:103366 )

• progressive loss of the thymus as mice age beginning at 2 weeks of age

thymus hypoplasia ( J:103366 )

• by 40 weeks of age mice have less than 1% of the number of thymocytes seen in heterozygous controls

growth/size/body

increased ear pigmentation ( J:103366 )

• darker ears compared to both agouti and black wild-type mice

enlarged spleen ( J:103366 )

• spleen is enlarged about 2.5- to 3.5-fold compared to wild-type mice due to expansion of the red pulp

spleen hyperplasia ( J:103366 )

• increase in the number of megakaryocytes, megakaryoblasts, and myelocytes but no increase in the number of lymphocytes is seen in the spleen

Genotype
MGI:3711320

ht3

• Allelic Composition: Cbl^tm1Ddlb/Cbl^tm2Wlan
• Genetic Background: involves: 129S1/Sv * C57BL/6

growth/size/body

decreased body weight ( J:121012 )

• mice weigh ~5% less than Cbl^tm1Ddlb heterozygous or wild-type male littermates at 18-24 weeks of age

decreased susceptibility to diet-induced obesity ( J:121012 )

adipose tissue

decreased brown adipose tissue amount ( J:121012 )

• brown fat mass is reduced ~20% relative to male Cbl^tm1Ddlb heterozygous littermates

decreased total body fat amount ( J:121012 )

• animals show ~25% reduction in fat mass compared to male Cbl^tm1Ddlb heterozygous or wild-type littermates

abnormal epididymal fat pad morphology ( J:121012 )

• epididymal fat mass is reduced ~33% compared with male Cbl^tm1Ddlb /+ heterozygous littermates

• high-fat fed mice have ~40% less epididymal fat mass than male Cbl^tm1Ddlb /+ heterozygous littermates

behavior/neurological

abnormal food intake ( J:121012 )

• mice have higher energy intake compared to male Cbl^tm1Ddlb /+ heterozygous littermates

homeostasis/metabolism

decreased susceptibility to diet-induced obesity ( J:121012 )

decreased circulating insulin level ( J:121012 )

• male mice show lower levels in fasted state and during the glucose tolerance test

• high-fat-fed male mice have ~45% lower circulating insulin levels than high-fat fed Cbl^tm1Ddlb /+ heterozygous littermates

decreased circulating leptin level ( J:121012 )

• levels are reduced ~55% (0.70 ng/ml vs 1.53 ng/ml in Cbl^tm1Ddlb /+ heterozygous littermates)

decreased circulating free fatty acids level ( J:121012 )

• levels are reduced ~20% (0.71 mmol/l vs 0.76 mmol/l in Cbl^tm1Ddlb /+ heterozygous littermates) at 18-24 weeks of age

decreased circulating triglyceride level ( J:121012 )

• levels are reduced relative to male Cbl^tm1Ddlb /+ heterozygous littermates (0.51 mmol/l vs 0.74 mmol/l)

increased oxygen consumption ( J:121012 )

• mice exhibit a 13% increase in whole body oxygen consumption compared to male Cbl^tm1Ddlb /+ heterozygous littermates)

• high-fat fed mice have ~10% higher oxygen consumption during the both light and dark phase than high-fat fed male Cbl^tm1Ddlb /+ heterozygous littermates at 18-24 weeks of age

improved glucose tolerance ( J:121012 )

• mice show significanty enhanced glucose clearance compared to Cbl^tm1Ddlb /+ heterozygous littermates 18-24 weeks old

• high-fat-fed male mice have a greater ability to clear glucose after intraperitoneal glucose injection than high-fat fed high-fat-fed Cbl^tm1Ddlb /+ heterozygous littermates; plasma glucose levels are close to basal levels within 90 minutes

increased insulin sensitivity ( J:121012 )

• in males, peripheral insulin sensitivity is increased compared to controls

abnormal enzyme/coenzyme activity ( J:121012 )

• cytochrome c oxidase and b-hydroxyacyl-CoA dehydrogenase activities are significantly elevated in skeletal muscle