Mouse Genome Informatics
cn
    Cdc42tm1Brak/Cdc42tm1Brak
Tg(Vil-cre)997Gum/0

involves: C57BL/6J * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• approximately 10% of mutants die at 6 months of age, with an average body weight of about 1/3 that of controls

growth/size/body
• mutants appear smaller in size starting at P9
• mutants become severely growth-retarded after weaning, with weight plateauing around 3 months of age

digestive/alimentary system
• at 3 months of age, mutants exhibit anal swelling, however no intestinal bleeding is seen
• at E16.5, intervillus epithelial cells display abnormalities in cytoplasmic division and nuclear organization
• postnatally, villus epithelial cells show an accumulation of vacuoles in their cytoplasm, which persists throughout adulthood with increased severity
• fetal and adult intestines show disruptions of basolateral plasma membrane in villus epithelia with frequent inclusions of lectin Dolichos biflorus agglutinin to the basolaterally located inter- or intracellular regions
• intestinal crypts contain increased numbers of enteroendocrine cells
• mutants exhibit formation of large intracellular vacuolar structures containing microvilli (microvillus inclusion bodies) in epithelial enterocytes as early as P7
• inclusion bodies become enlarged with age
• progenitor cells in intestinal crypts are intermingled and become indistinguishable from transit amplifying cells
• marker analysis indicates decreased stem and Paneth cell populations in crypts
• complete absence of typical Paneth cell granules in 99% of intestinal crypts at 1 month of age and marker analysis indicates decreased Paneth cell population in crypts
• intestinal crypts contain increased numbers of goblet cells
• soft stools are frequently detected at 3 months of age
• intestines show reduced nutrient uptake (of glucose, carnosine and proline), with almost no absorption of proline
• increase in number of cells undergoing mitosis in intestinal crypts
• increase in apoptotic cell number in intestinal crypts
• increase in intestinal tissue weight per surface area, indicating tissue edema

endocrine/exocrine glands
• progenitor cells in intestinal crypts are intermingled and become indistinguishable from transit amplifying cells
• marker analysis indicates decreased stem and Paneth cell populations in crypts
• complete absence of typical Paneth cell granules in 99% of intestinal crypts at 1 month of age and marker analysis indicates decreased Paneth cell population in crypts

cellular
• increase in apoptotic cell number in intestinal crypts

homeostasis/metabolism
• increase in intestinal tissue weight per surface area, indicating tissue edema

Mouse Models of Human Disease
OMIM IDRef(s)
Diarrhea 2, with Microvillus Atrophy; DIAR2 251850 J:184563