Phenotypes associated with this allele

• Allele Symbol: Hus1^tm1Led
• Allele Name: targeted mutation 1, Philip Leder
• Allele ID: MGI:1927769
• Summary: 6 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Hus1^tm1Led/Hus1^tm1Led	either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * Black Swiss)	MGI:2179049
hm2	Hus1^tm1Led/Hus1^tm1Led	involves: 129S6/SvEvTac	MGI:3590176
ht3	Hus1^tm1Led/Hus1^tm2Rsw	involves: 129S6/SvEvTac * C57BL/6	MGI:3702289
cn4	Hus1^tm1Led/Hus1^tm1Rsw Tg(Hsp70-1-cre)1Arge/0	involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * CBA	MGI:3590177
cx5	Hus1^tm1Led/Hus1^tm2Rsw Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:3702291
cx6	Cdkn1a^tm1Led/Cdkn1a^tm1Led Hus1^tm1Led/Hus1^tm1Led	involves: 129S6/SvEvTac	MGI:3590189

Genotype
MGI:2179049

hm1

• Allelic Composition: Hus1^tm1Led/Hus1^tm1Led
• Genetic Background: either: (involves: 129S6/SvEvTac) or (involves: 129S6/SvEvTac * Black Swiss)

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

mortality/aging

embryonic lethality during organogenesis, complete penetrance ( J:63869 )

• about 50% of embryos are alive at E9.5 and all are absent at E11.5

• Background Sensitivity: on a 129S6/SvEvTac background all embryos are dead by E9.5 compared to a mixed 129S6/SvEvTac and Black Swiss where about 50% of embryos are alive at E9.5

embryo

abnormal vitelline vasculature morphology ( J:63869 )

• the yolk sac lacks prominent vasculature at E9.5

increased embryonic tissue cell apoptosis ( J:63869 )

• increased numbers of apoptotic cells are seen in embryonic and extraembryonic tissues at E7.0 - E8.5; however, embryonic cell proliferation appears normal

failure of initiation of embryo turning ( J:63869 )

• at E8.5 embryos fail to initiate turning and at E9.5 still have not turned

embryonic growth retardation ( J:63869 )

• delayed development is seen at E8.5

decreased embryo size ( J:63869 )

• embryos are smaller than wild-type littermates at E7.5, E8.5, and E9.5

absent limb buds ( J:63869 )

• at E9.5 limb bud formation is not be detected

incomplete rostral neuropore closure ( J:63869 )

• at E9.5 the head folds usually fail to close

kinked neural tube ( J:63869 )

• seen at E9.5

abnormal somite development ( J:63869 )

• at E9.5 homozygous embryos have 8-13 somites compared to 20-24 in normal embryos

abnormal somite shape ( J:63869 )

abnormal allantois morphology ( J:63869 )

• in embryos where chorioallantoic fusion fails the allantois is located at the posterior of the embryo and appears swollen and bulbous

abnormal placenta labyrinth morphology ( J:63869 )

• the labyrinthine layer is abnormally compact

abnormal placental labyrinth vasculature morphology ( J:63869 )

• avascular

abnormal visceral yolk sac morphology ( J:63869 )

• at E9.5 the yolk sac appears thin and fragile

abnormal visceral yolk sac blood island morphology ( J:63869 )

• at E9.5, the blood islands contain mostly atypical, pyknotic cells

abnormal embryonic hematopoiesis ( J:63869 )

• few blood cells are seen at E9.5 in the yolk sac and none are found in the primitive umbilicus

failure of chorioallantoic fusion ( J:63869 )

• failure of chorioallantoic fusion is seen in 4 of 23 embryos

cellular

increased embryonic tissue cell apoptosis ( J:63869 )

• increased numbers of apoptotic cells are seen in embryonic and extraembryonic tissues at E7.0 - E8.5; however, embryonic cell proliferation appears normal

absent fibroblast proliferation ( J:63869 )

• homozygous MEFs fail to proliferate in culture

chromosome breakage ( J:63869 )

• increased chromosomal abnormalities are seen with 55% of metaphases from homozygous embryos displaying at least 1 abnormality compared to 19% of heterozygous and wild-type metaphases

• 44% of metaphases from homozygous embryos contain more than 1 aberration and 27% contain more than 5 aberrations

nervous system

incomplete rostral neuropore closure ( J:63869 )

• at E9.5 the head folds usually fail to close

kinked neural tube ( J:63869 )

• seen at E9.5

growth/size/body

embryonic growth retardation ( J:63869 )

• delayed development is seen at E8.5

decreased embryo size ( J:63869 )

• embryos are smaller than wild-type littermates at E7.5, E8.5, and E9.5

limbs/digits/tail

absent limb buds ( J:63869 )

• at E9.5 limb bud formation is not be detected

hematopoietic system

abnormal embryonic hematopoiesis ( J:63869 )

• few blood cells are seen at E9.5 in the yolk sac and none are found in the primitive umbilicus

cardiovascular system

abnormal placental labyrinth vasculature morphology ( J:63869 )

• avascular

abnormal vitelline vasculature morphology ( J:63869 )

• the yolk sac lacks prominent vasculature at E9.5

Genotype
MGI:3590176

hm2

• Allelic Composition: Hus1^tm1Led/Hus1^tm1Led
• Genetic Background: involves: 129S6/SvEvTac

embryo

increased embryonic tissue cell apoptosis ( J:99339 )

• increased numbers of apoptotic cells are seen in embryonic and extraembryonic tissues at E7.0 - E8.5; however, cell proliferation appears normal

abnormal developmental patterning ( J:99339 )

• the uniformity and symmetry seen in wild-type embryos is absent

embryonic growth retardation ( J:99339 )

• delayed development is seen in some embryos at E8.0

decreased embryo size ( J:99339 )

• embryos are slightly smaller than wild-type littermates at E7.5 and severely reduced in size by E8.5

abnormal neural tube morphology ( J:99339 )

• at E8.5 cell debris is seen in the neural tube

cellular

increased embryonic tissue cell apoptosis ( J:99339 )

• increased numbers of apoptotic cells are seen in embryonic and extraembryonic tissues at E7.0 - E8.5; however, cell proliferation appears normal

nervous system

abnormal neural tube morphology ( J:99339 )

• at E8.5 cell debris is seen in the neural tube

growth/size/body

embryonic growth retardation ( J:99339 )

• delayed development is seen in some embryos at E8.0

decreased embryo size ( J:99339 )

• embryos are slightly smaller than wild-type littermates at E7.5 and severely reduced in size by E8.5

Genotype
MGI:3702289

ht3

• Allelic Composition: Hus1^tm1Led/Hus1^tm2Rsw
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

cellular

abnormal chromosome morphology ( J:118898 )

• cultured mouse embryonic fibroblasts (MEFs) show an increased percentage of chromosomal aberrations compared to all other genotypes; by the third passage, 48% of metaphase spreads show at least one abnormality, while 32% have multiple abnormalities

• in vivo, mice show an elevated level of chromosomal instability compared to controls

abnormal cell physiology ( J:118898 )

• cells show reduced viability in response to treatment with amphidicolin; cells are 5-fold more sensitive to the replication inhibitor than Hus1^tm1Led /+ cells

abnormal cell cycle checkpoint function ( J:118898 )

• after BPDE treatment, DNA synthesis is maintained at 79.4% of untreated controls cultures, while Hus1^tm1Led/+ cultures show a reduction of DNA synthesis to 61.9% of control; this indicates that the S-phase damage checkpoint inhibiting DNA synthesis in response to genome damage is decreased in effectiveness

decreased cell proliferation ( J:118898 )

• MEFs from mutants show severely limited growth capacity compared to wild-type MEFs

chromosome breakage ( J:118898 )

• MEFs show a greater accumulation of double strand breaks after amphidicolin treatment than control cells with increased levels of chromatid interchanges

induced chromosome breakage ( J:118898 )

• MEFs show significantly increased sensitivity to DNA lesion-inducing agent BPDE; only 18.8% of cells remain viable 72 hours after treatment compared to 46% of heterozygous cells

oxidative stress ( J:118898 )

• treatment of cells with an antioxidant (NAC) almost completely suppresses the premature senescence

Genotype
MGI:3590177

cn4

• Allelic Composition: Hus1^tm1Led/Hus1^tm1Rsw; Tg(Hsp70-1-cre)1Arge/0
• Genetic Background: involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J * CBA

mortality/aging

prenatal lethality, incomplete penetrance ( J:99339 )

• fewer than expected mutants are found and those that do survive have little or no Cre-mediated recombination in most tissues with the exception of the lung and mammary gland where moderate levels of recombination are seen

Genotype
MGI:3702291

cx5

• Allelic Composition: Hus1^tm1Led/Hus1^tm2Rsw; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6

neoplasm

neoplasm ( J:118898 )

N • mice do not show differences in tumor development compared to wild-type Hus1, Trp53 heterozygotes

Genotype
MGI:3590189

cx6

• Allelic Composition: Cdkn1a^tm1Led/Cdkn1a^tm1Led; Hus1^tm1Led/Hus1^tm1Led
• Genetic Background: involves: 129S6/SvEvTac

cellular

increased cellular sensitivity to hydroxyurea ( J:63869 )

• double homozygous MEFs are 5- to 10-fold more sensitive to hydroxyurea compared to cells null for Cdkn1a only

increased cellular sensitivity to ultraviolet irradiation ( J:63869 )

• double homozygous MEFs are more sensitive to UV but not to ionizing radiation compared to cells null for Cdkn1a only

chromosome breakage ( J:63869 )

• mutant MEFs display increased numbers of chromosomal abnormalities; however unlike MEFs from Hus1 single homozygotes cells from 3 of 13 double homozygotes proliferated in culture