Phenotypes Associated with This Genotype

Genotype
MGI:4429602

• Allelic Composition: Msh2^tm1Htr/Msh2^tm1Htr
• Genetic Background: involves: 129P2/OlaHsd

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

mortality/aging

premature death ( J:45433 )

• two-third of mice die by 19.5 weeks

• Background Sensitivity: mice on a pure 129P2/OlaHsd background die sooner than those on a mixed 129P2/OlaHsd and FVB background

immune system

immune system phenotype ( J:47993 )

N • somatic hypermutation rates in memory B cells are normal

abnormal class switch recombination ( J:80893 )

• LPS-stimulated blasting B cells exhibit a 7-fold reduction in switching to IgG3 compared with similarly treated wild-type mice

• however, IgM response to LPS treatment is normal

abnormal somatic hypermutation frequency ( J:155454 )

• mice exhibit a 61% reduction in total mutation frequency in germinal center B cell compared with wild-type mice

decreased IgG1 level ( J:80893 )

• following NP-ficcoll or LPS plus IL4 stimulation

decreased IgG3 level ( J:80893 )

• following NP-ficcoll or LPS stimulation

abnormal inflammatory response ( J:80893 )

• LPS-stimulated blasting B cells exhibit a 7-fold reduction in switching to IgG3 compared with similarly treated wild-type mice

• however, the proportion of B cells that blasted in response to LPS is normal

neoplasm

increased tumor incidence ( J:45433 )

• mice that survive beyond 19.5 weeks exhibit a multitude of tumor types (lymphoid, erythroid, intestine, skin, sebaceous gland, brain, intestine, and hereditary nonpolyposis colorectal cancer)

increased gastrointestinal tumor incidence ( J:45433 )

• all mice that survive beyond 30 weeks develop HNPCC (hereditary nonpolyposis colorectal cancer)

increased skin tumor incidence ( J:45433 )

• in mice that survive beyond 19.5 weeks

increased lymphoma incidence ( J:45433 )

• 80% of mice that die prior to 19.5 weeks of age present with a lymphoid tumor, mostly of T cell origin

increased T cell derived lymphoma incidence ( J:45433 )

increased brain tumor incidence ( J:45433 )

• in 13% of mice that survive beyond 19.5 weeks

hematopoietic system

abnormal class switch recombination ( J:80893 )

• LPS-stimulated blasting B cells exhibit a 7-fold reduction in switching to IgG3 compared with similarly treated wild-type mice

• however, IgM response to LPS treatment is normal

abnormal somatic hypermutation frequency ( J:155454 )

• mice exhibit a 61% reduction in total mutation frequency in germinal center B cell compared with wild-type mice

decreased IgG1 level ( J:80893 )

• following NP-ficcoll or LPS plus IL4 stimulation

decreased IgG3 level ( J:80893 )

• following NP-ficcoll or LPS stimulation

integument

increased skin tumor incidence ( J:45433 )

• in mice that survive beyond 19.5 weeks

endocrine/exocrine glands

increased T cell derived lymphoma incidence ( J:45433 )

nervous system

increased brain tumor incidence ( J:45433 )

• in 13% of mice that survive beyond 19.5 weeks

digestive/alimentary system

increased gastrointestinal tumor incidence ( J:45433 )

• all mice that survive beyond 30 weeks develop HNPCC (hereditary nonpolyposis colorectal cancer)

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Lynch syndrome		DOID:3883	OMIM:PS120435	J:45433