Phenotypes Associated with This Genotype

Genotype
MGI:2663997

• Allelic Composition: Kit^tm2Bsm/Kit⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6J

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

mortality/aging

premature death ( J:83616 )

• starting at 4 weeks of age, heterozygotes develop symptoms of disease and eventually die from pathology in the GI tract, showing a 50% survival rate at 9 months of age

digestive/alimentary system

abnormal esophagus morphology ( J:83616 )

• 7 of 14 heterozygotes exhibit a well-defined, black-pigmented distal esophagus at the gastro-esophageal junction

• EM analysis indicates melanosomes, discontinuous external lamina, short cell processes, and single centrally located nucleoli

interstitial cells of Cajal hyperplasia ( J:83616 )

abnormal cecum morphology ( J:83616 )

• all (14 of 14) heterozygotes exhibit a firm white nodular mass of variable size (1 mm to 2 cm) in the cecum

distended cecum ( J:83616 )

• 9 of 14 heterozygotes display a distended cecum with clear fluid or pus-like contents

• atrophy of the colonic folds, lumen distension, and in one case abscess formation associated with acute serositis are observed

enlarged cecum ( J:83616 )

• 9 of 14 heterozygotes display an enlarged cecum

distended ileum ( J:83616 )

• 12 of 14 heterozygotes display variable distention of the distal ileum (mega-ileum) ending at the level of the cecum

• however, the remaining small intestine, stomach, colon, and anus appear morphologically normal

increased gastrointestinal stromal tumor incidence ( J:83616 )

• heterozygotes exhibit neoplastic lesions of GISTs predominantly in the myenteric plexus of the cecum

neoplasm

increased gastrointestinal stromal tumor incidence ( J:83616 )

• heterozygotes exhibit neoplastic lesions of GISTs predominantly in the myenteric plexus of the cecum

pigmentation

hyperpigmentation ( J:83616 )

• 7 of 14 heterozygotes display hypepigmentation of the distal esophagus at the gastro-esophageal junction

• 5 of 6 heterozygotes with a dark distal esophagus contain melanosomes specifically within the myenteric plexus

• pigmented areas of the esophageal myenteric plexus contain large, ovoid cells with abundant cytoplasm filled with numerous stage IV melanosomes, and are surrounded by a discontinuous linear basal lamina

• pigmented cells are intermixed with other cell components of the myenteric plexus, including Schwann cells, axonal processes, and interstitial cells of Cajal

immune system

increased mast cell degranulation ( J:83616 )

• heterozygotes exhibit extracellular granules in the vicinity of mast cells in the dorsal skin

increased mast cell number ( J:83616 )

• heterozygotes show a 4-fold increase in the number of mast cells in the dorsal skin and peritoneum

hematopoietic system

increased mast cell degranulation ( J:83616 )

• heterozygotes exhibit extracellular granules in the vicinity of mast cells in the dorsal skin

increased mast cell number ( J:83616 )

• heterozygotes show a 4-fold increase in the number of mast cells in the dorsal skin and peritoneum

reproductive system

reduced fertility ( J:83616 )

• both male and female heterozygotes are fertile but display a progressive decline in fertility with increasing age

nervous system

abnormal myenteric nerve plexus morphology ( J:83616 )

• all (6 of 6) heterozygotes display patchy hyperplasia of the myenteric plexus of the stomach, cecum and large intestine

• 3 of 6 heterozygotes display hyperplasia of the myenteric plexus in the proximal duodenum

• however, no myenteric plexus hyperplasia is observed in the morphologically normal distal duodenum, jejunum, and distended ileum

• in addition, 5 of 6 heterozygotes exhibit patchy thickening/hyperplasia of the esophageal myenteric plexus, and hyperpigmented cells are found specifically within the myenteric plexus of the of distal esophagus

cellular

increased mast cell degranulation ( J:83616 )

• heterozygotes exhibit extracellular granules in the vicinity of mast cells in the dorsal skin

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
gastrointestinal stromal tumor		DOID:9253	OMIM:606764	J:83616