Phenotypes associated with this allele

• Allele Symbol: Retnlb^tm1Lex
• Allele Name: targeted mutation 1, Lexicon Pharmaceuticals
• Allele ID: MGI:5007306
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Retnlb^tm1Lex/Retnlb^tm1Lex	B6.129S5-Retnlb^tm1Lex	MGI:6276254
hm2	Retnlb^tm1Lex/Retnlb^tm1Lex	FVB.129S5-Retnlb^tm1Lex	MGI:6276244

Genotype
MGI:6276254

hm1

• Allelic Composition: Retnlb^tm1Lex/Retnlb^tm1Lex
• Genetic Background: B6.129S5-Retnlb^tm1Lex

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

digestive/alimentary system

abnormal colon morphology ( J:235058 )

• colon hyperplasia, with increased colon thickness

• colonic expression of IL-13 and IFN-gamma are reduced under chow-fed conditions and expression of IL-13 is elevated under high-fat diet conditions

• colonic mRNA expression of serum amyloid A3 is increased

growth/size/body

growth/size/body region phenotype ( J:235058 )

N • Background Sensitivity: mice on a C57BL/6 background show inconsistent weight differences unlike mice on an FVB/N background which show increased weight

homeostasis/metabolism

impaired glucose tolerance ( J:235058 )

• mice show reduced glucose tolerance, even in the absence of a dietary challenge and/or obesity

• glucose intolerance is most pronounced in mice that show the thickest colons, regardless of weight

decreased incidence of tumors by chemical induction ( J:235058 )

• Background Sensitivity: mice on the C57BL/6 background barely develop colon tumors when treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) unlike mice on the FVB background that show increased susceptibility to induced colorectal cancer

neoplasm

decreased incidence of tumors by chemical induction ( J:235058 )

• Background Sensitivity: mice on the C57BL/6 background barely develop colon tumors when treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) unlike mice on the FVB background that show increased susceptibility to induced colorectal cancer

Genotype
MGI:6276244

hm2

• Allelic Composition: Retnlb^tm1Lex/Retnlb^tm1Lex
• Genetic Background: FVB.129S5-Retnlb^tm1Lex

adipose tissue

increased mesenteric fat pad weight ( J:235058 )

• significant increase in mesenteric adipose tissue weight relative to body weight

white adipose tissue inflammation ( J:235058 )

• increase in mRNA expression of inflammatory markers in mesenteric white adipose tissue

digestive/alimentary system

abnormal colon morphology ( J:235058 )

• colon hyperplasia, with increased colon length and weight

• antibiotic treated mice show reduced colon weight and length from 23% and 22%, respectively, to 14% and 9%

growth/size/body

increased body weight ( J:235058 )

• Background Sensitivity: mice on the FVB/N background are slightly heavier, even on a normal chow diet compared to inconsistent weight differences on a C57BL/6 background

• degree of obesity/weight gain is positively associated with glucose intolerance

enlarged liver ( J:235058 )

• mild hepatomegaly

hematopoietic system

increased neutrophil cell number ( J:235058 )

• AOM/DSS-treated mice have a higher number of total IL-13+ and Gr1/Ly6G+ leukocytes and Gr1/Ly6G+IL-13+ cells in mesenteric lymph nodes and tumors, indicating increased number of IL-13-producting neutrophils

• however, the number of IFNgamma+ and CD4+ lymphocytes is similar to controls

abnormal CD4-positive, alpha-beta T cell physiology ( J:235058 )

• AOM/DSS-treated mice show a skewed Th1-Th2 cytokine balance, showing elevated Th2-type cytokines (IL-13, IL-4, IL-5) and IL-17 colonic expression and increased levels of the Th2 differentiation marker GATA3, indicating a dominant type 2 immune response

• AOM only treated mice also show higher colonic expression of IL-13, IL-5, IL-10, and IL-17 than in controls

homeostasis/metabolism

increased circulating interleukin-13 level ( J:235058 )

• although serum IL-13 levels are similar to wild-type levels during the AOM/DSS time course, acute serum IL-13 levels after 7 days 4% DSS treatment are higher in mutants than controls

decreased circulating interleukin-6 level ( J:235058 )

• serum IL-6 levels are decreased by day 85 after AOM/DSS treatment compared to wild-type mice

impaired glucose tolerance ( J:235058 )

• mice are severely glucose intolerant

• ablating the gut microbiota with antibiotic treatment protects the mice against metabolic disturbances, restoring glucose tolerance

increased incidence of tumors by chemical induction ( J:235058 )

• Background Sensitivity: mice on the FVB/N background treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) exhibit an increase in both the number and size of colon tumors compared to wild-type controls or mutant mice on the C57BL/6 background, indicating increased susceptibility to induced colorectal cancer

• mice injected only with AOM develop fewer tumors than when treated with an AOM/DSS combination but still about twice as many tumors as wild-type controls

immune system

white adipose tissue inflammation ( J:235058 )

• increase in mRNA expression of inflammatory markers in mesenteric white adipose tissue

increased neutrophil cell number ( J:235058 )

• AOM/DSS-treated mice have a higher number of total IL-13+ and Gr1/Ly6G+ leukocytes and Gr1/Ly6G+IL-13+ cells in mesenteric lymph nodes and tumors, indicating increased number of IL-13-producting neutrophils

• however, the number of IFNgamma+ and CD4+ lymphocytes is similar to controls

abnormal CD4-positive, alpha-beta T cell physiology ( J:235058 )

• AOM/DSS-treated mice show a skewed Th1-Th2 cytokine balance, showing elevated Th2-type cytokines (IL-13, IL-4, IL-5) and IL-17 colonic expression and increased levels of the Th2 differentiation marker GATA3, indicating a dominant type 2 immune response

• AOM only treated mice also show higher colonic expression of IL-13, IL-5, IL-10, and IL-17 than in controls

increased circulating interleukin-13 level ( J:235058 )

• although serum IL-13 levels are similar to wild-type levels during the AOM/DSS time course, acute serum IL-13 levels after 7 days 4% DSS treatment are higher in mutants than controls

decreased circulating interleukin-6 level ( J:235058 )

• serum IL-6 levels are decreased by day 85 after AOM/DSS treatment compared to wild-type mice

liver inflammation ( J:235058 )

• increase in mRNA expression of inflammatory markers in the liver

liver/biliary system

enlarged liver ( J:235058 )

• mild hepatomegaly

liver inflammation ( J:235058 )

• increase in mRNA expression of inflammatory markers in the liver

neoplasm

increased incidence of tumors by chemical induction ( J:235058 )

• Background Sensitivity: mice on the FVB/N background treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) exhibit an increase in both the number and size of colon tumors compared to wild-type controls or mutant mice on the C57BL/6 background, indicating increased susceptibility to induced colorectal cancer

• mice injected only with AOM develop fewer tumors than when treated with an AOM/DSS combination but still about twice as many tumors as wild-type controls