Phenotypes associated with this allele

• Allele Symbol: Atm^tm1Fwa
• Allele Name: targeted mutation 1, Frederick W Alt
• Allele ID: MGI:1933748
• Summary: 5 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atm^tm1Fwa/Atm^tm1Fwa	involves: 129S4/SvJae	MGI:5463808
hm2	Atm^tm1Fwa/Atm^tm1Fwa	involves: 129S4/SvJae * C57BL/6	MGI:2175707
cx3	Atm^tm1Fwa/Atm^tm1Fwa H2ax^tm1Fwa/H2ax^tm1Fwa	involves: 129S4/SvJae * 129S6/SvEvTac	MGI:3851149
cx4	Atm^tm1Fwa/Atm^tm1Fwa Pknox1^tm1Fbla/Pknox1^+	involves: 129S4/SvJae * C57BL/6	MGI:4839470
cx5	Atm^tm1Fwa/Atm^tm1Fwa Pknox1^tm1Fbla/Pknox1^tm1Fbla	involves: 129S4/SvJae * C57BL/6	MGI:4839471

Genotype
MGI:5463808

hm1

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

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

mortality/aging

mortality/aging ( J:191288 )

N • mice are born in Mendelian ratios

cellular

chromosomal instability ( J:191288 )

• embryonic stem cells exhibit increased spontaneous cytogenetic abnormalities (predominantly chromosome breaks) compared with wild-type cells

• B cells from tamoxifen-treated mice exhibit reduced class switch recombination with increased genomic instability compared with wild-type cells

immune system

abnormal class switch recombination ( J:191288 )

• B cells from tamoxifen-treated mice exhibit reduced class switch recombination with increased genomic instability compared with wild-type cells

hematopoietic system

abnormal class switch recombination ( J:191288 )

• B cells from tamoxifen-treated mice exhibit reduced class switch recombination with increased genomic instability compared with wild-type cells

Genotype
MGI:2175707

hm2

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

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

Genotype
MGI:3851149

cx3

• Allelic Composition: Atm^tm1Fwa/Atm^tm1Fwa; H2ax^tm1Fwa/H2ax^tm1Fwa
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:138190 )

• because the two genes are 4 cm apart, the cross of heterozygote parents resulted in a 4% cross-over frequency of which half (2%) of the cross-overs had the two null alleles linked

• breeding of these progeny resulted in embryonic lethality in the double homozygotes

• half the embryos are dead at E11.5 and all embryos dead by E12.5

• embryos had pleiotropic developmental defects associated with increased cell death and decreased mitotic index

cellular

increased cell death ( J:138190 )

• freshly isolated E10.5 MEFs have a dramatic increase in the sub-G1 population, indicative of massive cell death

chromosomal instability ( J:138190 )

• 80% of E10.5 MEFs have cytogenetic abnormalities compared to 2-3% in wild-type controls

spontaneous chromosome breakage ( J:138190 )

• MEF metaphases contained numerous breaks per metaphase (average more than three abnormalities per abnormal metaphase), in contrast to one or, rarely, two aberrations per abnormal metaphase for controls

Genotype
MGI:4839470

cx4

• Allelic Composition: Atm^tm1Fwa/Atm^tm1Fwa; Pknox1^tm1Fbla/Pknox1⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6

embryo

embryonic growth retardation ( J:165811 )

• in 2 of 4 mice

growth/size/body

embryonic growth retardation ( J:165811 )

• in 2 of 4 mice

Genotype
MGI:4839471

cx5

• Allelic Composition: Atm^tm1Fwa/Atm^tm1Fwa; Pknox1^tm1Fbla/Pknox1^tm1Fbla
• Genetic Background: involves: 129S4/SvJae * C57BL/6

mortality/aging

embryonic lethality between implantation and somite formation, incomplete penetrance ( J:165811 )

• only one mouse is recovered at E7.5

embryo

embryonic growth retardation ( J:165811 )

• in the single mouse generated

abnormal pluripotent precursor cell morphology ( J:165811 )

• at E7.5, Oct4+ cells are almost undetectable in the single mouse generated

growth/size/body

embryonic growth retardation ( J:165811 )

• in the single mouse generated