Phenotypes associated with this allele

• Allele Symbol: B3gnt6^tm1Lx
• Allele Name: targeted mutation 1, Lijun Xia
• Allele ID: MGI:5447022
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	B3gnt6^tm1Lx/B3gnt6^tm1Lx	involves: 129S1/Sv * C57BL/6J	MGI:5447023
cn2	B3gnt6^tm1Lx/B3gnt6^tm1Lx C1galt1^tm1.1Rpmc/C1galt1^tm1.1Rpmc Tg(Vil1-cre/ERT2)23Syr/0	involves: 129S1/Sv * C57BL/6 * C57BL/6J * DBA/2	MGI:5902497
cn3	B3gnt6^tm1Lx/B3gnt6^tm1Lx C1galt1^tm1.1Rpmc/C1galt1^tm1.1Rpmc Tg(Vil1-cre)997Gum/0	involves: 129S1/Sv * C57BL/6J * SJL	MGI:5902495

Genotype
MGI:5447023

hm1

• Allelic Composition: B3gnt6^tm1Lx/B3gnt6^tm1Lx
• Genetic Background: involves: 129S1/Sv * C57BL/6J

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

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:123826 )

• greater in DSS-treated mice

digestive/alimentary system

rectal hemorrhage ( J:123826 )

• greater fetal bleeding in DSS-treated mice

abnormal enterocyte proliferation ( J:123826 )

• increased proliferation of colonic epithelial crypt cells in mice treated with azoxymethane and DSS

abnormal intestinal mucosa morphology ( J:123826 )

• mice exhibit impaired mucosal integrity in the colon

abnormal crypts of Lieberkuhn morphology ( J:123826 )

• greater severe crypt destruction in DSS-treated mice

intestinal ulcer ( J:123826 )

• greater in DSS-treated mice

decreased colon length ( J:123826 )

• greater shortening of colon length in DSS-treated mice

increased gastrointestinal tumor incidence ( J:123826 )

• mice treated with azoxymethane and DSS exhibit accelerated colorectal tumorigenesis with increased tumor volume compared with wild-type mice

increased intestinal adenoma incidence ( J:123826 )

• occasionally in mice treated with azoxymethane and DSS

diarrhea ( J:123826 )

• greater in DSS-treated mice

increased susceptibility to induced colitis ( J:123826 )

• DSS-treated mice exhibit increased severity of colitis with greater weight loss, diarrhea, fecal bleeding, shortened colon length, severe crypt destruction, larger areas of epithelial ulceration, erosions, massive inflammatory cell infiltration (T cells and monocytes/macrophages) into the mucosal tissue, increased intracellular expression of IL2, IFNgamma and TNF-alpha in CD4+ T cells, and increased lethality compared with wild-type mice

neoplasm

increased gastrointestinal tumor incidence ( J:123826 )

• mice treated with azoxymethane and DSS exhibit accelerated colorectal tumorigenesis with increased tumor volume compared with wild-type mice

increased intestinal adenoma incidence ( J:123826 )

• occasionally in mice treated with azoxymethane and DSS

increased incidence of tumors by chemical induction ( J:123826 )

• mice treated with azoxymethane and DSS exhibit accelerated colorectal tumorigenesis with increased tumor volume and proliferation of colonic epithelial crypt cells compared with wild-type mice

increased tumor growth/size ( J:123826 )

• increased tumor volume in mice treated with azoxymethane and DSS

increased carcinoma incidence ( J:123826 )

• intramucosal carcinoma in mice treated with azoxymethane and DSS

increased adenocarcinoma incidence ( J:123826 )

• some adenomas progress to adenocarcinomas that invade muscularis mucosae and submucosa in mice treated with azoxymethane and DSS

immune system

increased susceptibility to induced colitis ( J:123826 )

• DSS-treated mice exhibit increased severity of colitis with greater weight loss, diarrhea, fecal bleeding, shortened colon length, severe crypt destruction, larger areas of epithelial ulceration, erosions, massive inflammatory cell infiltration (T cells and monocytes/macrophages) into the mucosal tissue, increased intracellular expression of IL2, IFNgamma and TNF-alpha in CD4+ T cells, and increased lethality compared with wild-type mice

increased T cell number ( J:123826 )

• greater infiltration into the lamina propria in DSS-treated mice

increased macrophage cell number ( J:123826 )

• greater infiltration into the lamina propria in DSS-treated mice

increased monocyte cell number ( J:123826 )

• greater infiltration into the lamina propria in DSS-treated mice

increased interferon-gamma secretion ( J:123826 )

• greater in the CD4+ T cells of DSS-treated mice

increased interleukin-2 secretion ( J:123826 )

• greater in the CD4+ T cells of DSS-treated mice

increased tumor necrosis factor secretion ( J:123826 )

• greater in the CD4+ T cells of DSS-treated mice

growth/size/body

increased susceptibility to weight loss ( J:123826 )

• greater in DSS-treated mice

cardiovascular system

rectal hemorrhage ( J:123826 )

• greater fetal bleeding in DSS-treated mice

cellular

abnormal enterocyte proliferation ( J:123826 )

• increased proliferation of colonic epithelial crypt cells in mice treated with azoxymethane and DSS

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:123826 )

• greater severe crypt destruction in DSS-treated mice

hematopoietic system

increased T cell number ( J:123826 )

• greater infiltration into the lamina propria in DSS-treated mice

increased macrophage cell number ( J:123826 )

• greater infiltration into the lamina propria in DSS-treated mice

increased monocyte cell number ( J:123826 )

• greater infiltration into the lamina propria in DSS-treated mice

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:123826 )

• greater in DSS-treated mice

increased incidence of tumors by chemical induction ( J:123826 )

• mice treated with azoxymethane and DSS exhibit accelerated colorectal tumorigenesis with increased tumor volume and proliferation of colonic epithelial crypt cells compared with wild-type mice

Genotype
MGI:5902497

cn2

• Allelic Composition: B3gnt6^tm1Lx/B3gnt6^tm1Lx; C1galt1^tm1.1Rpmc/C1galt1^tm1.1Rpmc; Tg(Vil1-cre/ERT2)23Syr/0
• Genetic Background: involves: 129S1/Sv * C57BL/6 * C57BL/6J * DBA/2

digestive/alimentary system

increased duodenum glandular epithelium tumor incidence ( J:239765 )

• mice injected with tamoxifen at 1.5- to 4-months of age develop spontaneous duodenal tumors between 12 and 24 months of age, exhibiting mostly proliferative epithelium

increased duodenum adenocarcinoma incidence ( J:239765 )

• tumors in tamoxifen-injected mice are aggressive and advance to adenocarcinoma

neoplasm

increased duodenum glandular epithelium tumor incidence ( J:239765 )

• mice injected with tamoxifen at 1.5- to 4-months of age develop spontaneous duodenal tumors between 12 and 24 months of age, exhibiting mostly proliferative epithelium

increased duodenum adenocarcinoma incidence ( J:239765 )

• tumors in tamoxifen-injected mice are aggressive and advance to adenocarcinoma

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
duodenum cancer		DOID:10021		J:23965

Genotype
MGI:5902495

cn3

• Allelic Composition: B3gnt6^tm1Lx/B3gnt6^tm1Lx; C1galt1^tm1.1Rpmc/C1galt1^tm1.1Rpmc; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: 129S1/Sv * C57BL/6J * SJL

digestive/alimentary system

abnormal intestinal mucosa morphology ( J:239765 )

• duodenal mucosa is slightly thicker at 5 months of age

abnormal small intestine morphology ( J:239765 )

• moderate thickening in different regions of the small intestinal tract is seen in a subset of mutants that are 12-20 months of age

• thickening of the small intestine is most pronounced in the proximal duodenum

abnormal duodenum morphology ( J:239765 )

• loss of acidic glycans, such as sialic acid and sulfated mucin, and presence of neutral structures, such as Tn antigen in duodenal mucosa

• little secreted mucus is seen in luminal regions or between villi of 5 month old mice

• duodenal mucosa is slightly thicker and the villi wider at 5 months of age

• administration of broad spectrum antibiotics does not increase luminal mucus in the duodenum and does not increase villus spacing

abnormal duodenum crypts of Lieberkuhn morphology ( J:239765 )

• expansion in the proliferative zone of the duodenal crypt in 4 and 8 month old mice

duodenal lesions ( J:239765 )

• numerous lesions within the first 2 cm of the duodenum; these regions are composed of hyperplastic duodenal mucosa overlaying submucosal Brunners glands

• lesions are devoid of villous structures and contain dysplastic epithelium, suggesting adenomatous polyps

abnormal ileum morphology ( J:239765 )

• 30% of mice exhibit thickening in the terminal ileum, although no tumor development is seen in this region

abnormal small intestinal villus morphology ( J:239765 )

• villi are less spaced apart than in wild-type mice and are usually adherent to each other

• duodenal villi are wider at 5 months of age

increased duodenum glandular epithelium tumor incidence ( J:239765 )

• approximately 27% of mice develop spontaneous duodenal tumors, with an average of 4 lesions per mouse, by about 1 year of age

• tumors are epithelial cell-derived

• tumor incidence does not increase with age but aggressiveness of tumors increases over time

small intestinal inflammation ( J:239765 )

• modest spontaneous duodenal inflammation at 5 months of age, with a modest influx of polymorphonuclear cells and leukocytes into the mucosa

endocrine/exocrine glands

abnormal duodenum crypts of Lieberkuhn morphology ( J:239765 )

• expansion in the proliferative zone of the duodenal crypt in 4 and 8 month old mice

immune system

small intestinal inflammation ( J:239765 )

• modest spontaneous duodenal inflammation at 5 months of age, with a modest influx of polymorphonuclear cells and leukocytes into the mucosa

neoplasm

increased duodenum glandular epithelium tumor incidence ( J:239765 )

• approximately 27% of mice develop spontaneous duodenal tumors, with an average of 4 lesions per mouse, by about 1 year of age

• tumors are epithelial cell-derived

• tumor incidence does not increase with age but aggressiveness of tumors increases over time

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
duodenum cancer		DOID:10021		J:239765