Phenotypes Associated with This Genotype

Genotype
MGI:3833153

• Allelic Composition: Brca2^tm1Kamc/Brca2^tm1Kamc
• Genetic Background: involves: 129P2/OlaHsd * BALB/c

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

mortality/aging

increased mortality induced by ionizing radiation ( J:144998 )

• all mice die within 5 to 9 days of exposure to a dose at which 90% of wild-type mice survive

hematopoietic system

abnormal hematopoietic system morphology/development ( J:144998 )

• unlike in wild-type mice, wild-type transplanted cells engraft and reconstitute close to 45% after 6 months

decreased common myeloid progenitor cell number ( J:144998 )

• colony forming cells are decreased 25% to 50% in the bone marrow and spleen of adult and 1.5 week old mice compared to in wild-type mice

• only 12% of bone marrow cells form large colonies compared to 45% of wild-type cells

• the reduction in colony forming cells is more marked as length of incubation in culture is increased

impaired hematopoiesis ( J:144998 )

• following whole body irradiation, mice exhibit leukopenia, anemia, and thrombopenia that are more severe and last longer than in similarly treated wild-type mice

• when subjected to a competitive repopulation assay, bone marrow cells exhibit reduced hematopoiesis compared to wild-type cells

• bone marrow cells maintained under physiological steady-state conditions exhibit impaired hematopoiesis compared to wild-type cells

decreased bone marrow cell number ( J:144998 )

• femoral bone marrow cellularity is slightly reduced compared to in wild-type mice

• however, this decrease may reflect the decrease in body weight

spleen hypoplasia ( J:144998 )

• spleen cellularity is slightly reduced compared to in wild-type mice

• however, this decrease may reflect the decrease in body weight

cellular

abnormal chromosome morphology ( J:144998 )

• bone marrow cells exhibit a high number of spontaneous chromatid breaks compared to wild-type cells

• bone marrow cells exposed to 30 nM mitomycin C exhibit more chromatid breaks that similarly treated wild-type cells

increased sensitivity to induced cell death ( J:144998 )

• colony forming cells are more sensitive to mitomycin C than wild-type cells

• however, dosage values for X-ray exposed cells is normal, and cells from mice transplanted with wild-type cells exhibit a partial rescue of mitomycin C sensitivity

abnormal DNA repair ( J:144998 )

• no Rad51 foci are apparent in fibroblasts exposed to 12 Gy radiation unlike in similarly treated wild-type cells

growth/size/body

decreased body weight ( J:144998 )

• by 15%

immune system

spleen hypoplasia ( J:144998 )

• spleen cellularity is slightly reduced compared to in wild-type mice

• however, this decrease may reflect the decrease in body weight

homeostasis/metabolism

abnormal DNA repair ( J:144998 )

• no Rad51 foci are apparent in fibroblasts exposed to 12 Gy radiation unlike in similarly treated wild-type cells

increased mortality induced by ionizing radiation ( J:144998 )

• all mice die within 5 to 9 days of exposure to a dose at which 90% of wild-type mice survive

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi anemia complementation group D1		DOID:0111089	OMIM:605724	J:144998