Phenotypes Associated with This Genotype

Genotype
MGI:3615592

• Allelic Composition: Muc2^wnn/Muc2^wnn
• Genetic Background: C57BL/6-Muc2^wnn

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

Fewer goblet cells in the intestines of Muc2^wnn/Muc2^wnn mice and reduction in secreted mucus

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:194148 )

• lethal ulcerating colitis in DSS-treated mice

premature death ( J:194148 )

• at 1 year, some mice die or are euthanized due to rectal prolapse or debility

digestive/alimentary system

abnormal intestinal mucosa morphology ( J:194148 )

• reduced mucus secretion

abnormal intestinal goblet cell morphology ( J:104190 , J:194148 )

• homozygous mutant mice develop goblet cell hyperplasia (J:104190)

• fewer goblet cells in the small and large intestines due to increased apoptosis with smaller thecae (J:194148)

abnormal large intestine crypts of Lieberkuhn morphology ( J:194148 )

• increased crypt length in the cecum and distal large intestine with increased intestinal proliferation and apoptosis

intestinal ulcer ( J:194148 )

• lethal ulcerating colitis in DSS-treated mice

abnormal colon morphology ( J:194148 )

• progressive increase in proximal and distal colon thickness and weight from 6 to 18 weeks

decreased colon length ( J:194148 )

• decreased colon length in DSS-treated mice

• however, colon length is not shortened in untreated mice

rectal prolapse ( J:104190 , J:194148 )

• some homozygous mice develop rectal prolapse (J:104190)

• in some mice (J:194148)

abnormal digestive system physiology ( J:194148 )

• 2.5-fold increase in the proportion of fecal bacteria coated in immunoglobulin

diarrhea ( J:104190 )

• homozygous mice have soft feces at weaning and later develop diarrhea

abnormal intestinal absorption ( J:104190 )

• mutant mice exhibit malabsorption syndrome

melena ( J:194148 )

• in DSS-treated mice

abnormal intestine physiology ( J:194148 )

• increased intestinal permeability

increased enterocyte apoptosis ( J:194148 )

• in distal large intestine

abnormal enterocyte proliferation ( J:194148 )

• increased in distal large intestine

colitis ( J:194148 )

• mild colitis at 6, 12 and 18 weeks with crypt elongation, neutrophilic infiltrates, goblet cell loss, crypt abscesses, and focal epithelial erosions

increased susceptibility to induced colitis ( J:194148 )

• in DSS-treated mice with rapid weight loss and lethal ulcerating colitis

ileum inflammation ( J:194148 )

• in DSS-treated mice

immune system

colitis ( J:194148 )

• mild colitis at 6, 12 and 18 weeks with crypt elongation, neutrophilic infiltrates, goblet cell loss, crypt abscesses, and focal epithelial erosions

increased susceptibility to induced colitis ( J:194148 )

• in DSS-treated mice with rapid weight loss and lethal ulcerating colitis

ileum inflammation ( J:194148 )

• in DSS-treated mice

increased leukocyte cell number ( J:194148 )

• in DSS-treated mice

• 5-fold increase in leukocytes in the mesenteric lymph nodes in untreated mice

increased lymphocyte cell number ( J:194148 )

• in DSS-treated mice

increased interferon-gamma secretion ( J:194148 )

• from mesenteric lymph node leukocytes stimulated with PMA and ionomycin

increased interleukin-1 beta secretion ( J:194148 )

• from distal colon explants

increased interleukin-13 secretion ( J:194148 )

• from mesenteric lymph node leukocytes stimulated with PMA and ionomycin

increased tumor necrosis factor secretion ( J:194148 )

• from distal colon explants

• from mesenteric lymph node leukocytes stimulated with PMA and ionomycin

growth/size/body

increased susceptibility to weight loss ( J:194148 )

• in DSS-treated mice

cellular

abnormal intestinal goblet cell morphology ( J:104190 , J:194148 )

• homozygous mutant mice develop goblet cell hyperplasia (J:104190)

• fewer goblet cells in the small and large intestines due to increased apoptosis with smaller thecae (J:194148)

abnormal endoplasmic reticulum morphology ( J:194148 )

• distended cells with membranous vacuolar material in the large intestine

• goblet cells possess dilated rough endoplasmic reticulum

abnormal mitochondrial crista morphology ( J:194148 )

• swollen mitochondria with disrupted cristae in the large intestine

dilated mitochondrion ( J:194148 )

• swollen mitochondria with disrupted cristae in the large intestine

increased enterocyte apoptosis ( J:194148 )

• in distal large intestine

abnormal enterocyte proliferation ( J:194148 )

• increased in distal large intestine

increased endoplasmic reticulum stress ( J:194148 )

• aberrant mucin assembly triggers an endoplasmic reticulum stress response and unfolded protein response activation

endocrine/exocrine glands

abnormal large intestine crypts of Lieberkuhn morphology ( J:194148 )

• increased crypt length in the cecum and distal large intestine with increased intestinal proliferation and apoptosis

homeostasis/metabolism

increased circulating triglyceride level ( J:194148 )

• in DSS-treated mice

increased susceptibility to xenobiotic induced morbidity/mortality ( J:194148 )

• lethal ulcerating colitis in DSS-treated mice

hematopoietic system

decreased hematocrit ( J:194148 )

• in DSS-treated mice

increased leukocyte cell number ( J:194148 )

• in DSS-treated mice

• 5-fold increase in leukocytes in the mesenteric lymph nodes in untreated mice

increased lymphocyte cell number ( J:194148 )

• in DSS-treated mice

neoplasm

neoplasm ( J:194148 )

N • unlike Muc2^tm1Avel, mice do not develop spontaneous intestinal tumors

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
inflammatory bowel disease		DOID:0050589	OMIM:PS266600	J:194148