Mouse Genome Informatics
ht
    Kittm2Bsm/Kit+
involves: 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
       
mortality/aging
• 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
• 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
• all (14 of 14) heterozygotes exhibit a firm white nodular mass of variable size (1 mm to 2 cm) in the cecum
• 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
• 9 of 14 heterozygotes display an enlarged cecum
• 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

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

pigmentation
• 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
• heterozygotes show a 4-fold increase in the number of mast cells in the dorsal skin and peritoneum
• heterozygotes exhibit extracellular granules in the vicinity of mast cells in the dorsal skin

hematopoietic system
• heterozygotes show a 4-fold increase in the number of mast cells in the dorsal skin and peritoneum
• heterozygotes exhibit extracellular granules in the vicinity of mast cells in the dorsal skin

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

nervous system
• 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

Mouse Models of Human Disease
OMIM IDRef(s)
Gastrointestinal Stromal Tumor; GIST 606764 J:83616