Mouse Genome Informatics
hm1
    Atmtm1Bal/Atmtm1Bal
involves: 129S4/SvJae
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Electron micrographs of wild type and Atmtm1Bal/Atmtm1Bal Purkinje neurons

mortality/aging
• animals with thymic lymphomas die by 4 months of age due to size of tumor that disrupts the thoracic cavity

growth/size/body
• homozygous mice weigh approximately 88% of controls at 3 weeks of age; the weight is 75% of controls at 5 weeks of age and persists through adulthood

cellular
• 72 hours after serum stimulation, starved MEFs have reduced numbers of cells in S phase compared to controls, indicating a defect in cell cycle progression
• homozygous ES cells have a reduced survival rate compared to controls when exposed to increasing dosages of gamma-irradiation
• homozygous MEFs exhibited defective cell cycle arrest rates and decreased up-regulation of Trp53 following gamma-irradiation, and exhibited a
• mutant thymocytes are more resistant to gamma-irradiation induced apoptosis than control cells
• homozygous MEFs grow slowly in culture and achieve senesence by passage 6

tumorigenesis
• tumors form in almost all mice by 3 months of age, and are often seen in 1-2 month old animals

reproductive system
• ovaries are degenerate and contain no primary oocytes or follicles (J:35914)
(J:35914)
• meiosis is disrupted prior to normal meiotic arrest in females (J:35914)
• development appears to arrest between the zygotene and pachytene stages of meiotic prophase (J:35914)
• spermatocytes are found in various stages of degeneration and round or elongated spermatids are absent (J:35914)
(J:35914)

immune system
• 60% decrease in the single positive and double positive thymocyte subpopulations
• particular reduction in the proportion of CD4+ single positive thymocytes
• decreased number of B220+IgM- pre-B cells in the bone marrow (63% of controls)
• similar numbers of B220+CD43+ pre-B cells are present compared to controls
• similar numbers of B cells are seen in the spleen when compared to controls
• a 1.5-2 fold decrease in serum levels of IgG2a, IgG2b and IgG3 is seen
• T cell-dependent immune respose to NP15-CG is impaired in homozygous mice
• T cell-independent immune responses are similar to controls
• widespread microglial activation associated with neuronal loss

nervous system
• widespread microglial activation associated with neuronal loss
• 21% exhibit degenerating granule cells
• 46.5% exhibit degenerating neurons in the molecular layer
• although earlier studies using light microscopy did not reveal neuron degeneration, detailed electron microscopy reveals widespread neuronal degeneration and glial activation
• 33% exhibit degenerating/dystrophic Purkinje cells

behavior/neurological
N
• no ataxia or other behavioral abnormalities are seen (J:35914)

endocrine/exocrine glands
• ovaries are degenerate and contain no primary oocytes or follicles (J:35914)
• 60% decrease in the single positive and double positive thymocyte subpopulations
• particular reduction in the proportion of CD4+ single positive thymocytes

hematopoietic system
• 60% decrease in the single positive and double positive thymocyte subpopulations
• particular reduction in the proportion of CD4+ single positive thymocytes
• decreased number of B220+IgM- pre-B cells in the bone marrow (63% of controls)
• similar numbers of B220+CD43+ pre-B cells are present compared to controls
• similar numbers of B cells are seen in the spleen when compared to controls
• a 1.5-2 fold decrease in serum levels of IgG2a, IgG2b and IgG3 is seen
• T cell-dependent immune respose to NP15-CG is impaired in homozygous mice
• T cell-independent immune responses are similar to controls
• widespread microglial activation associated with neuronal loss

Mouse Models of Human Disease
OMIM IDRef(s)
Ataxia-Telangiectasia; AT 208900 J:42324 , J:44190