Phenotypes associated with this allele

• Allele Symbol: Fancd2^tm1Hou
• Allele Name: targeted mutation 1, Scott Houghtaling
• Allele ID: MGI:2673422
• Summary: 10 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Fancd2^tm1Hou/Fancd2^tm1Hou	129S4/SvJae-Fancd2^tm1Hou	MGI:2673460
hm2	Fancd2^tm1Hou/Fancd2^tm1Hou	B6.129S4-Fancd2^tm1Hou	MGI:2673459
hm3	Fancd2^tm1Hou/Fancd2^tm1Hou	involves: 129S4/SvJae	MGI:3804707
hm4	Fancd2^tm1Hou/Fancd2^tm1Hou	involves: 129S4/SvJae * C57BL/6J	MGI:2673461
cx5	Brip1^Gt(RRI409)Byg/Brip1^Gt(RRI409)Byg Fancd2^tm1Hou/Fancd2^tm1Hou	involves: 129P2/OlaHsd * 129S4/SvJae	MGI:5771655
cx6	Dclre1a^tm1Remo/Dclre1a^tm1Remo Fancd2^tm1Hou/Fancd2^tm1Hou	involves: 129S4/SvJae * 129X1/SvJ * C57BL/6J	MGI:3804706
cx7	Aldh2^tm1a(EUCOMM)Wtsi/Aldh2^tm1a(EUCOMM)Wtsi Fancd2^tm1Hou/Fancd2^+	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:5467972
cx8	Aldh2^tm1a(EUCOMM)Wtsi/Aldh2^+ Fancd2^tm1Hou/Fancd2^tm1Hou	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:5467973
cx9	Aldh2^tm1a(EUCOMM)Wtsi/Aldh2^tm1a(EUCOMM)Wtsi Fancd2^tm1Hou/Fancd2^tm1Hou	involves: 129S4/SvJae * C57BL/6J * C57BL/6N	MGI:5467971
cx10	Fan1^tm1d(KOMP)Wtsi/Fan1^tm1d(KOMP)Wtsi Fancd2^tm1Hou/Fancd2^tm1Hou	involves: 129S4/SvJae * C57BL/6N * FVB/N	MGI:5897865

Genotype
MGI:2673460

hm1

• Allelic Composition: Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: 129S4/SvJae-Fancd2^tm1Hou

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

neoplasm

increased adenoma incidence ( J:84892 )

• observed in both on a 129S4/SvJae genetic background and on a background involving both 129S4/SvJae and C57BL/6J

increased carcinoma incidence ( J:84892 )

• observed in both on a 129S4/SvJae genetic background and on a background involving both 129S4/SvJae and C57BL/6J

cellular

oligozoospermia ( J:84892 )

♂

abnormal spermatocyte morphology ( J:84892 )

♂ • apoptotic pachytene spermatocytes observed in some seminiferous tubules

endocrine/exocrine glands

abnormal ovarian follicle number ( J:84892 )

♀ • reduced number of developing follicles

abnormal seminiferous tubule morphology ( J:84892 )

♂ • incomplete penetrance of abnormal tubules either lacking germ cells or containing apoptotic spermatocytes

small testis ( J:84892 )

♂

reproductive system

oligozoospermia ( J:84892 )

♂

abnormal spermatocyte morphology ( J:84892 )

♂ • apoptotic pachytene spermatocytes observed in some seminiferous tubules

abnormal ovarian follicle number ( J:84892 )

♀ • reduced number of developing follicles

abnormal seminiferous tubule morphology ( J:84892 )

♂ • incomplete penetrance of abnormal tubules either lacking germ cells or containing apoptotic spermatocytes

small testis ( J:84892 )

♂

abnormal male meiosis ( J:84892 )

♂ • increased frequency of synaptic abnormalities beginning in mid-zygotene

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi anemia complementation group D2		DOID:0111083	OMIM:227646	J:84892

Genotype
MGI:2673459

hm2

• Allelic Composition: Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: B6.129S4-Fancd2^tm1Hou

mortality/aging

perinatal lethality, incomplete penetrance ( J:84892 )

• a significant deviation from expected Mendelian ratios was observed 5 days after birth on a C57BL/6J genetic background

• expected Mendelian ratios were observed 5 days after birth on a 129S4/SvJae genetic background

growth/size/body

decreased body weight ( J:84892 )

• observed on a C57Bl/6J genetic background but not on a 129S4/SvJae genetic background

postnatal growth retardation ( J:84892 )

• Background Sensitivity: observed on a C57Bl/6J genetic background but not on a 129S4/SvJae genetic background

fetal growth retardation ( J:84892 )

• reduced body size observed several days after birth indicated delayed development in utero

vision/eye

microphthalmia ( J:84892 )

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi anemia complementation group D2		DOID:0111083	OMIM:227646	J:84892

Genotype
MGI:3804707

hm3

• Allelic Composition: Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: involves: 129S4/SvJae

mortality/aging

mortality/aging ( J:134461 )

N • partial perinatal lethality is not observed as reported by others possibly due to a higher percentage of 129S4/SvJae background in the breeding stock

reproductive system

infertility ( J:193232 )

cellular

increased sensitivity to induced cell death ( J:188123 , J:193232 )

• B cells, erythroid progenitor and granulocyte-macrophage progenitor cells are more sensitive to acetaldehyde (J:188123)

• B cells treated with LPS and increasing amounts of acetaldehyde exhibit reduced survival compared with control cells (J:193232)

hematopoietic system

decreased hematopoietic stem cell number ( J:188123 )

• young mice show a 2-fold reduction in the LKS population

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:188123 )

• B cells, erythroid progenitor and granulocyte-macrophage progenitor cells are more sensitive to acetaldehyde

Genotype
MGI:2673461

hm4

• Allelic Composition: Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

neoplasm

increased adenoma incidence ( J:84892 )

• observed in both on a 129S4/SvJae genetic background and on a background involving both 129S4/SvJae and C57BL/6J

increased carcinoma incidence ( J:84892 )

• observed in both on a 129S4/SvJae genetic background and on a background involving both 129S4/SvJae and C57BL/6J

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi anemia complementation group D2		DOID:0111083	OMIM:227646	J:84892

Genotype
MGI:5771655

cx5

• Allelic Composition: Brip1^{Gt(RRI409)Byg}/Brip1^{Gt(RRI409)Byg}; Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae

reproductive system

abnormal seminiferous tubule morphology ( J:227115 )

♂ • histology revealed significantly more atrophic seminiferous tubules relative to single homozygotes and wild-type controls

♂ • atrophic tubules are mostly devoid of spermatogenic cells and composed of Sertoli cells only

small testis ( J:227115 )

♂ • double mutants show significantly smaller testes than wild-type controls

cellular

increased cellular sensitivity to DNA damaging agents ( J:227115 )

• unexpectedly, MEFs derived from double homozygotes are significantly more sensitive to mitomycin C than either single homozygote

endocrine/exocrine glands

abnormal seminiferous tubule morphology ( J:227115 )

♂ • histology revealed significantly more atrophic seminiferous tubules relative to single homozygotes and wild-type controls

♂ • atrophic tubules are mostly devoid of spermatogenic cells and composed of Sertoli cells only

small testis ( J:227115 )

♂ • double mutants show significantly smaller testes than wild-type controls

Genotype
MGI:3804706

cx6

• Allelic Composition: Dclre1a^tm1Remo/Dclre1a^tm1Remo; Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: involves: 129S4/SvJae * 129X1/SvJ * C57BL/6J

mortality/aging

perinatal lethality, incomplete penetrance ( J:134461 )

• 33% less double homozygotes are born than expected

• Background Sensitivity: the expected number of double homozygotes are observed when the breeding stock has a higher percentage of 129 background

Genotype
MGI:5467972

cx7

• Allelic Composition: Aldh2^{tm1a(EUCOMM)Wtsi}/Aldh2^{tm1a(EUCOMM)Wtsi}; Fancd2^tm1Hou/Fancd2⁺
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N

cellular

maternal effect ( J:193232 )

♀ • despite expected ratios at E9.5, all offspring die by E13.5 when dams are Aldh2^{tm1a(EUCOMM)Wtsi} homozygotes

♀ • however, offspring are produced when dams are Aldh2^{tm1a(EUCOMM)Wtsi} heterozygotes

Genotype
MGI:5467973

cx8

• Allelic Composition: Aldh2^{tm1a(EUCOMM)Wtsi}/Aldh2⁺; Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N

nervous system

exencephaly ( J:193232 )

• in mice exposed to ethanol at E7.5 unlike control mice

vision/eye

abnormal eye morphology ( J:193232 )

• in mice exposed to ethanol at E7.5 unlike control mice

Genotype
MGI:5467971

cx9

• Allelic Composition: Aldh2^{tm1a(EUCOMM)Wtsi}/Aldh2^{tm1a(EUCOMM)Wtsi}; Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: involves: 129S4/SvJae * C57BL/6J * C57BL/6N

mortality/aging

increased susceptibility to xenobiotic induced morbidity/mortality ( J:193232 )

• fewer than expected mice are present at E16.5 following in utero exposure to ethanol at E7.5

premature death ( J:193232 )

• unexposed mice succumb to an acute illness (weight loss and lethargy) within 3 to 6 months

embryonic lethality during organogenesis ( J:193232 )

• despite expected ratios at E9.5, all offspring die by E13.5 when dams are Aldh2^{tm1a(EUCOMM)Wtsi} homozygotes despite no effect on offpsring heterozygous for the allele

immune system

abnormal thymus morphology ( J:188123 )

• the nucleated cellularity of the thymus is decreased in 8-12 week old mice

abnormal lymphopoiesis ( J:193232 )

• blast-like lymphoid cells in the peripheral blood film and bone marrow aspirate in unexposed mice

increased double-positive T cell number ( J:193232 )

• in three instances in unexposed mice

increased CD8-positive, alpha-beta T cell number ( J:193232 )

• in one instance in an unexposed mice

decreased leukocyte cell number ( J:188123 )

• in 8-12 week old mice

abnormal spleen morphology ( J:188123 )

• the nucleated cellularity of the spleen is decreased in 8-12 week old mice

enlarged spleen ( J:193232 )

• in unexposed mice

neoplasm

increased acute lymphoblastic leukemia incidence ( J:193232 )

• in unexposed mice

increased lymphoma incidence ( J:193232 )

• in most unexposed mice

increased T cell derived lymphoma incidence ( J:193232 )

• in some unexposed mice

growth/size/body

decreased body weight ( J:193232 )

• in unexposed mice

weight loss ( J:193232 )

• in unexposed mice

abnormal chest morphology ( J:193232 )

• most unexposed mice develop large mediastinal mass

enlarged spleen ( J:193232 )

• in unexposed mice

vision/eye

abnormal eye morphology ( J:193232 )

• unexposed mice exhibit eye abnormalities unlike control mice

• in utero exposure to ethanol increased the prevalence of eye abnormalities compared to in control mice

anophthalmia ( J:193232 )

• mice exposed to ethanol at E7.5 unlike control mice

nervous system

exencephaly ( J:193232 )

• mice exposed to ethanol at E7.5 unlike control mice

behavior/neurological

lethargy ( J:193232 )

• in unexposed mice

homeostasis/metabolism

increased susceptibility to xenobiotic induced morbidity/mortality ( J:193232 )

• fewer than expected mice are present at E16.5 following in utero exposure to ethanol at E7.5

increased physiological sensitivity to xenobiotic ( J:188123 )

• B cells, erythroid progenitor and granulocyte-macrophage progenitor cells are more sensitive to acetaldehyde than wild-type cells, but no more sensitive than single Fancd2 homozygotes

limbs/digits/tail

kinked tail ( J:193232 )

• in unexposed mice

hematopoietic system

abnormal thymus morphology ( J:188123 )

• the nucleated cellularity of the thymus is decreased in 8-12 week old mice

abnormal lymphopoiesis ( J:193232 )

• blast-like lymphoid cells in the peripheral blood film and bone marrow aspirate in unexposed mice

increased double-positive T cell number ( J:193232 )

• in three instances in unexposed mice

extramedullary hematopoiesis ( J:188123 )

• aged mice that do not develop leukemia show extramedullary hematopoiesis

anemia ( J:188123 , J:193232 )

• aged mice that do not develop leukemia spontaneously develop aplastic anemia, with accumulation of damaged DNA within the hematopoietic stem and progenitor cell pool (J:188123)

• in 6 to 8 week old mice exposed to ethanol (J:193232)

impaired hematopoiesis ( J:193232 )

• almost complete obliteration of bone marrow hematopoiesis in 6 to 8 week old mice exposed to ethanol

abnormal bone marrow cell morphology/development ( J:193232 )

• from bone marrow of 6 to 8 week old mice exposed to ethanol produces fewer progenitor colony-forming units corresponding to pre-B cells, granulocytes and erythrocytes compared with control mice

decreased bone marrow cell number ( J:188123 , J:193232 )

• the nucleated cellularity of whole bone marrow is decreased in 8-12 week old mice (J:188123)

• of nucleated cells in 6 to 8 week old mice exposed to ethanol (J:193232)

decreased erythrocyte cell number ( J:188123 , J:193232 )

• in 8-12 week old mice (J:188123)

• young mice, however exhibit normal T cell, B cell, myeloid, and erythroid differentiation (J:188123)

• in 6 to 8 week old mice exposed to ethanol (J:193232)

decreased hematocrit ( J:188123 )

• in 8-12 week old mice

decreased hemoglobin content ( J:188123 , J:193232 )

• in 8-12 week old mice (J:188123)

• in 6 to 8 week old mice exposed to ethanol (J:193232)

increased mean corpuscular volume ( J:188123 )

• young mice exhibit an increase in the mean corpuscular volume of erythrocytes

thrombocytopenia ( J:188123 )

• in 8-12 week old mice

increased CD8-positive, alpha-beta T cell number ( J:193232 )

• in one instance in an unexposed mice

decreased leukocyte cell number ( J:188123 )

• in 8-12 week old mice

decreased hematopoietic stem cell number ( J:188123 )

• young mice that have not develop leukemia show a 30-fold reduction in the LKS population, 10-fold reduction in the frequency of LT-HSCs (Lin- c-Kit+ Sca-1+ Flt3- CD34-), and a 251-fold reduction in the frequency of HSCs (Lin- CD41- CD48- CD150+ c-Kit+ Sca-1+) in the bone marrow

pancytopenia ( J:188123 )

• aged mice that do not develop leukemia show pancytopenia

abnormal spleen morphology ( J:188123 )

• the nucleated cellularity of the spleen is decreased in 8-12 week old mice

enlarged spleen ( J:193232 )

• in unexposed mice

abnormal hematopoietic stem cell physiology ( J:188123 )

• accumulation in the S-G2-M phase of the cell cycle in long term hematopoietic stem cells (LT-HSCs)

• reduction in the number of quiescent (G0) LT-HSCs, with the majority actively cycling

endocrine/exocrine glands

abnormal thymus morphology ( J:188123 )

• the nucleated cellularity of the thymus is decreased in 8-12 week old mice

increased T cell derived lymphoma incidence ( J:193232 )

• in some unexposed mice

cellular

increased sensitivity to induced cell death ( J:188123 )

• B cells, erythroid progenitor and granulocyte-macrophage progenitor cells are more sensitive to acetaldehyde than wild-type cells, but no more sensitive than single Fancd2 homozygotes

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
Fanconi anemia complementation group D2		DOID:0111083	OMIM:227646	J:193232

Genotype
MGI:5897865

cx10

• Allelic Composition: Fan1^{tm1d(KOMP)Wtsi}/Fan1^{tm1d(KOMP)Wtsi}; Fancd2^tm1Hou/Fancd2^tm1Hou
• Genetic Background: involves: 129S4/SvJae * C57BL/6N * FVB/N

homeostasis/metabolism

increased physiological sensitivity to xenobiotic ( J:232402 )

• MEFs are more sensitive to mitomycin C induced proliferation defects compared to cells from mice homozygous for Fan1 alone but similar to cells from mice homozygous for Fancd2 alone

• increase in the degree of mitomycin C induced chromosomal abnormalities in MEFs compared to Fancd2 single homozygous MEFs

hematopoietic system

abnormal hematopoietic stem cell morphology ( J:232402 )

• loss of Fan1 does not increase the severity of hematopoietic stem cell defects compared to mice homozygous for the Fancd2 mutation alone