Phenotypes Associated with This Genotype

Genotype
MGI:3590232

• Allelic Composition: Apc^tm1Kk/Apc^tm1Kk; Tg(Lck-cre)1Cwi/?
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6 * DBA/2

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

immune system

small thymus ( J:100461 )

thymus hypoplasia ( J:100461 )

• 1/8 to 1/10 as many thymocytes as in controls

abnormal T cell differentiation ( J:100461 )

• higher levels of apoptosis in DN3, DN4, and DP cells

increased double-negative T cell number ( J:100461 )

• 50% of thymocytes with a double negative phenotype

arrested T cell differentiation ( J:100461 )

• T cell development is blocked at the DN4 stage

increased mast cell number ( J:128606 )

• total mononuclear cell preparations from the intestine shows at least a 9-fold higher frequency of mast cell progenitors than wild-type mice

• treatment of mice with anti-TNFalpha antibody lowers the numbers of mast cell progenitors in the intestine

increased circulating tumor necrosis factor level ( J:128606 )

• 10-fold increase in serum TNFalpha levels by 4 months of age but declines to 3-fold increase in late-stage polyposis

hematopoietic system

small thymus ( J:100461 )

thymus hypoplasia ( J:100461 )

• 1/8 to 1/10 as many thymocytes as in controls

abnormal T cell differentiation ( J:100461 )

• higher levels of apoptosis in DN3, DN4, and DP cells

increased double-negative T cell number ( J:100461 )

• 50% of thymocytes with a double negative phenotype

arrested T cell differentiation ( J:100461 )

• T cell development is blocked at the DN4 stage

increased mast cell number ( J:128606 )

• total mononuclear cell preparations from the intestine shows at least a 9-fold higher frequency of mast cell progenitors than wild-type mice

• treatment of mice with anti-TNFalpha antibody lowers the numbers of mast cell progenitors in the intestine

endocrine/exocrine glands

small thymus ( J:100461 )

thymus hypoplasia ( J:100461 )

• 1/8 to 1/10 as many thymocytes as in controls

digestive/alimentary system

abnormal intestinal mucosa morphology ( J:104334 )

• dysplastic crypts with hyperchromatic nuclei, expanding at the luminal surface of the mucosa, neighboring well spaced, nondysplastic crypts and villi

intestine polyps ( J:128606 )

• intestinal lesions are seen as early as 2 months after birth and mice develop adenomatous polyps that are typically infiltrated with intraepithelial mast cells restricted to the lesions

• mice treated with anti-TNFalpha antibody every 2 days for 2 weeks show fewer polyps than controls and the polyps that persist have a more flattened and differentiated morphology and are smaller, and the mean vessel volume in the polyps is 4-times less than in untreated mice

increased intestinal adenoma incidence ( J:104334 )

• mice show adenomas in the small and large intestine from 2 months of age which typically have a tubovillous appearance

• adenomas are devoid of differentiated cells

homeostasis/metabolism

increased circulating tumor necrosis factor level ( J:128606 )

• 10-fold increase in serum TNFalpha levels by 4 months of age but declines to 3-fold increase in late-stage polyposis

neoplasm

increased intestinal adenoma incidence ( J:104334 )

• mice show adenomas in the small and large intestine from 2 months of age which typically have a tubovillous appearance

• adenomas are devoid of differentiated cells

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
familial adenomatous polyposis		DOID:0050424	OMIM:PS175100	J:128606