Phenotypes Associated with This Genotype

Genotype
MGI:2175707

• Allelic Composition: Atm^tm1Fwa/Atm^tm1Fwa
• Genetic Background: involves: 129S4/SvJae * C57BL/6

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

Dendritic changes in Purkinje cells of Atm^tm1Fwa/Atm^tm1Fwa mice

mortality/aging

premature death ( J:61201 )

• death in mice carrying thymic lymphomas occcurs by 4-5 months of age

• 50% of mice survive 10 months or more

growth/size/body

decreased body weight ( J:61201 )

• approximately a 20% reduction in body weight is observed

postnatal growth retardation ( J:61201 )

neoplasm

increased T cell derived lymphoma incidence ( J:61201 )

• T cell-derived lymphomas frequently resulted in premature death

immune system

increased T cell derived lymphoma incidence ( J:61201 )

• T cell-derived lymphomas frequently resulted in premature death

decreased lymphocyte cell number ( J:61201 )

• only 40-50% of the normal levels of thymocytes and splenocytes are seen

decreased immature B cell number ( J:61201 )

• reduced numbers of immature B cells in bone marrow

decreased pre-B cell number ( J:61201 )

• reduced numbers of precursor B cells in bone marrow

• mature B cell numbers are similar to controls

decreased T cell number ( J:61201 )

• 8-10 fold reduction in splenic T cell numbers

decreased thymocyte number ( J:61201 )

• 2-fold decrease in double positive and a 5-fold decrease in single positive thymocytes

decreased splenocyte number ( J:61201 )

• only 40-50% of the normal levels of splenocytes are seen

behavior/neurological

abnormal motor learning ( J:61201 )

• mice do not exhibit improvement over time on the accelerating rotarod test

decreased locomotor activity ( J:61201 )

• adult mice tend to explore an open field less than controls

nervous system

abnormal Purkinje cell axon morphology ( J:61201 )

• Purkinje cell axons exhibit varicosities in the internal granule cell layer; however, these swellings are small and unlike the large axonal swellings seen in human Ataxia-Telangiectasia patients

abnormal Purkinje cell dendrite morphology ( J:61201 )

• irregular pattern of dendrites; consistently branch prematurely and have multiple dendrites originating from one cell body

• dendrites often project at odd angles in the molecular layer

ectopic Purkinje cell ( J:61201 )

• Purkinje cell bodies are seen in the molecular layer

thin cerebellar molecular layer ( J:61201 )

• the cerebellum molecular layer is approximately 13% thinner than controls

reproductive system

female infertility ( J:61201 )

♀

male infertility ( J:61201 )

♂

cellular

increased cellular sensitivity to gamma-irradiation ( J:61201 )

• homozygous cells were hypersensitive to irradiation (data not shown)

hematopoietic system

increased T cell derived lymphoma incidence ( J:61201 )

• T cell-derived lymphomas frequently resulted in premature death

decreased lymphocyte cell number ( J:61201 )

• only 40-50% of the normal levels of thymocytes and splenocytes are seen

decreased immature B cell number ( J:61201 )

• reduced numbers of immature B cells in bone marrow

decreased pre-B cell number ( J:61201 )

• reduced numbers of precursor B cells in bone marrow

• mature B cell numbers are similar to controls

decreased T cell number ( J:61201 )

• 8-10 fold reduction in splenic T cell numbers

decreased thymocyte number ( J:61201 )

• 2-fold decrease in double positive and a 5-fold decrease in single positive thymocytes

decreased splenocyte number ( J:61201 )

• only 40-50% of the normal levels of splenocytes are seen

endocrine/exocrine glands

decreased thymocyte number ( J:61201 )

• 2-fold decrease in double positive and a 5-fold decrease in single positive thymocytes

increased T cell derived lymphoma incidence ( J:61201 )

• T cell-derived lymphomas frequently resulted in premature death

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
ataxia telangiectasia		DOID:12704	OMIM:208900	J:61201