Phenotypes Associated with This Genotype

Genotype
MGI:8332042

• Allelic Composition: Braf^tm1Mmcm/Braf⁺; X/Tg(Myh11-icre/ERT2)1Soff
• Genetic Background: involves: 129P2/OlaHsd * C57BL/6J * FVB/N

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

cellular

interstitial cells of Cajal hyperplasia ( J:300991 )

• mice treated with a small dose of tamoxifen show rapid onset of interstitial cells of Cajal (ICC) hyperplasia

digestive/alimentary system

interstitial cells of Cajal hyperplasia ( J:300991 )

• mice treated with a small dose of tamoxifen show rapid onset of interstitial cells of Cajal (ICC) hyperplasia

abnormal stomach wall morphology ( J:300991 )

• mice treated with a small dose of tamoxifen exhibit a gastric wall that is largely composed of smooth muscle with hyperplastic stromal cells

abnormal stomach muscularis externa morphology ( J:300991 )

• proliferating cells are seen in smooth muscle, which are rarely seen in wild-type smooth muscle

increased gastrointestinal stromal tumor incidence ( J:300991 )

• mice treated with a small dose of tamoxifen at 6 weeks of age exhibit gastric lesions that are diffusely CD34+ and PDGFRA+, indicating gastrointestinal stromal tumors (GIST)

• less prominent lesions are seen in the small and large intestinal wall of tamoxifen-treated mice

• 4 of 11 mice treated with an even lower dose of tamoxifen at 6 weeks of age, develop tumors in the smooth muscle layer of the gut and bladder 4 months after tamoxifen; tumors are solid and devoid of a lumen, have a spindle-shaped cellular morphology with an appearance of dedifferentiated GIST

mortality/aging

decreased tumor-free survival time ( J:300991 )

• mice become moribund within 1-2 weeks after a standard dose of tamoxifen, possibly due to impaired gut motility

• one month after a single small dose of tamoxifen, mice appear moribund; an even lower dose of tamoxifen prolongs survival further

muscle

abnormal stomach muscularis externa morphology ( J:300991 )

• proliferating cells are seen in smooth muscle, which are rarely seen in wild-type smooth muscle

neoplasm

increased gastrointestinal stromal tumor incidence ( J:300991 )

• mice treated with a small dose of tamoxifen at 6 weeks of age exhibit gastric lesions that are diffusely CD34+ and PDGFRA+, indicating gastrointestinal stromal tumors (GIST)

• less prominent lesions are seen in the small and large intestinal wall of tamoxifen-treated mice

• 4 of 11 mice treated with an even lower dose of tamoxifen at 6 weeks of age, develop tumors in the smooth muscle layer of the gut and bladder 4 months after tamoxifen; tumors are solid and devoid of a lumen, have a spindle-shaped cellular morphology with an appearance of dedifferentiated GIST

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
gastrointestinal stromal tumor		DOID:9253	OMIM:606764	J:300991