Phenotypes Associated with This Genotype

Genotype
MGI:6392094

• Allelic Composition: Fancd2^em1Tzh/Fancd2^em1Tzh
• Genetic Background: C57BL/6-Fancd2^em1Tzh

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

mortality/aging

postnatal lethality, incomplete penetrance ( J:284566 )

• 30% of pups with growth retardation gradually die of progressive asthenia around and after weaning

prenatal lethality, incomplete penetrance ( J:284566 )

• pups are born at a lower rate than expected, with only 5.5% versus the expected 25% of pups seen at P14

growth/size/body

decreased body size ( J:284566 )

• P60 mice are slightly smaller

postnatal growth retardation ( J:284566 )

• 30% of pups show severe growth retardation

enlarged spleen ( J:284566 )

behavior/neurological

weakness ( J:284566 )

• 30% of pups with growth retardation gradually die of progressive asthenia around and after weaning

endocrine/exocrine glands

abnormal ovarian follicle morphology ( J:284566 )

• ovaries show only interstitial cells and no follicle structures

small ovary ( J:284566 )

abnormal testis morphology ( J:284566 )

• testes show aberrant tubules

small testis ( J:284566 )

hematopoietic system

enlarged spleen ( J:284566 )

abnormal erythropoiesis ( J:284566 )

• the R2 (basophilic erythroblasts) and R3 (chromatophilic erythroblasts) stage immature erythroblasts are reduced in the bone marrow, indicating impaired basal state erythropoiesis

• increase in the R1-R4 (proerythroblasts, basophilic erythroblasts, chromatophilic erythroblasts, and orthochromatophilic erythroblasts) stage immature erythroblasts in the spleen, suggesting stressed erythropoiesis in the spleen

anemia ( J:284566 )

• mice show progressive anemia

abnormal bone marrow cell morphology/development ( J:284566 )

• reduction in the frequencies of hematopoietic stem cell-enriched myeloid progenitor compartment

• bone marrow contains 1/2 the numbers of myeloid progenitor cells and 1/3 of LSK cells compared to wild-type

• bone marrow shows a severe deficit in the long-term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs) and multi-potent progenitors (MPPs)

• however, frequencies if mature myeloid cells (Gr1+CD11b+) or lymphoid cells (B220+ or CD3e+) are normal in the bone marrow

decreased erythroblast number ( J:284566 )

• the R2 (basophilic erythroblasts) and R3 (chromatophilic erythroblasts) stage immature erythroblasts are reduced in the bone marrow, indicating impaired basal state erythropoiesis

increased erythroblast number ( J:284566 )

• increase in the R1-R4 (proerythroblasts, basophilic erythroblasts, chromatophilic erythroblasts, and orthochromatophilic erythroblasts) stage immature erythroblasts in the spleen, suggesting stressed erythropoiesis in the spleen

decreased erythrocyte cell number ( J:284566 )

• red blood cell count is reduced in 2-month-old mice

decreased hemoglobin content ( J:284566 )

• slight, but significant, reduction in hemoglobin level

• however, white blood cell counts, platelets and mean corpuscular volume level are normal

decreased hematopoietic stem cell number ( J:284566 )

• reduction in the frequencies of hematopoietic stem cell-enriched LSK compartment

• bone marrow contains 1/3 of LSK cells compared to wild-type bone marrow

• bone marrow shows a severe deficit in the long-term hematopoietic stem cells (LT-HSCs), short-term HSCs (ST-HSCs) and multi-potent progenitors (MPPs)

abnormal hematopoietic stem cell physiology ( J:284566 )

• bone marrow progenitor cells show elevated cell death, apoptosis, and G2-M phase accumulation at baseline and upon Mitomycin C treatment

immune system

enlarged spleen ( J:284566 )

reproductive system

azoospermia ( J:284566 )

• testes show total absence of germ cells

abnormal ovarian follicle morphology ( J:284566 )

• ovaries show only interstitial cells and no follicle structures

small ovary ( J:284566 )

abnormal testis morphology ( J:284566 )

• testes show aberrant tubules

small testis ( J:284566 )

vision/eye

abnormal lens development ( J:284566 )

• 2 month old eyes show lack of lens development

aphakia ( J:284566 )

• 90% of mice exhibit aphakia or microphthalmia

abnormal retina development ( J:284566 )

• 2 month old eyes show lack of retina chamber development

microphthalmia ( J:284566 )

• 90% of mice exhibit aphakia or microphthalmia

cellular

azoospermia ( J:284566 )

• testes show total absence of germ cells

increased cellular sensitivity to ionizing radiation ( J:284566 )

• bone marrow progenitor cells show increased cell death and G2-M phase arrest after ionizing radiation treatment

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi anemia complementation group D2		DOID:0111083	OMIM:227646	J:284566