Phenotypes Associated with This Genotype

Genotype
MGI:5427868

• Allelic Composition: Cdc42^tm1Brak/Cdc42^tm1Brak; Tg(Vil1-cre)997Gum/0
• Genetic Background: involves: C57BL/6J * SJL

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

mortality/aging

premature death ( J:184563 )

• 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

decreased body size ( J:184563 )

• mutants appear smaller in size starting at P9

postnatal growth retardation ( J:184563 )

• mutants become severely growth-retarded after weaning, with weight plateauing around 3 months of age

digestive/alimentary system

abnormal anus morphology ( J:184563 )

• at 3 months of age, mutants exhibit anal swelling, however no intestinal bleeding is seen

abnormal intestine morphology ( J:184563 )

abnormal intestinal goblet cell morphology ( J:184563 )

• intestinal crypts contain increased numbers of goblet cells

abnormal intestinal enteroendocrine cell morphology ( J:184563 )

• intestinal crypts contain increased numbers of enteroendocrine cells

abnormal intestinal epithelium morphology ( J:184563 )

• 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

abnormal enterocyte morphology ( J:184563 )

• 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

abnormal crypts of Lieberkuhn morphology ( J:184563 )

• 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

decreased Paneth cell number ( J:184563 )

• 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 edema ( J:184563 )

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

abnormal defecation ( J:184563 )

• soft stools are frequently detected at 3 months of age

abnormal intestine physiology ( J:184563 )

• intestines show reduced nutrient uptake (of glucose, carnosine and proline), with almost no absorption of proline

abnormal small intestinal crypt cell physiology ( J:184563 )

• increase in number of cells undergoing mitosis in intestinal crypts

increased small intestinal crypt cell apoptosis ( J:184563 )

• increase in apoptotic cell number in intestinal crypts

endocrine/exocrine glands

abnormal crypts of Lieberkuhn morphology ( J:184563 )

• 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

decreased Paneth cell number ( J:184563 )

• 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

abnormal intestinal goblet cell morphology ( J:184563 )

• intestinal crypts contain increased numbers of goblet cells

increased small intestinal crypt cell apoptosis ( J:184563 )

• increase in apoptotic cell number in intestinal crypts

homeostasis/metabolism

intestinal edema ( J:184563 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
microvillus inclusion disease		DOID:0060775	OMIM:251850	J:184563