Phenotypes associated with this allele

• Allele Symbol: Dkc1^tm1.1Pjma
• Allele Name: targeted mutation 1.1, Philip J Mason
• Allele ID: MGI:3809481
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Dkc1^tm1.1Pjma/Dkc1^+	involves: 129X1/SvJ * C57BL/6 * FVB/N	MGI:3809484
ot2	Dkc1^tm1.1Pjma/Y	B6.129X1(FVB)-Dkc1^tm1.1Pjma	MGI:5644816
ot3	Dkc1^tm1.1Pjma/Y	involves: 129X1/SvJ * C57BL/6 * FVB/N	MGI:3809483

Genotype
MGI:3809484

ht1

• Allelic Composition: Dkc1^tm1.1Pjma/Dkc1⁺
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * FVB/N

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

hematopoietic system

abnormal hematopoietic system morphology/development ( J:138335 )

♀ • cells in spleen, thymus, bone marrow, and peripheral blood expressing the wild-type protein have a growth advantage over cells expressing the mutant protein

Genotype
MGI:5644816

ot2

• Allelic Composition: Dkc1^tm1.1Pjma/Y
• Genetic Background: B6.129X1(FVB)-Dkc1^tm1.1Pjma

cellular

abnormal cell physiology ( J:217050 )

♂ • marker analysis indicates an increase in DNA damage in the liver, spleen and bone marrow

decreased fibroblast proliferation ( J:217050 )

♂ • growth rate of MEFs is lower when cultured at both ambient oxygen (21%) and low (3%) oxygen, with cells growing more slowly in 21% oxygen and cells growing more slowly and entering senescence earlier than wild-type cells in 3% oxygen

♂ • decreased growth rates of MEFs are associated with increased ROS levels and increased accumulation of DNA damage

decreased hematopoietic stem cell proliferation ( J:217050 )

♂ • competitive and serial bone marrow transplantation experiments indicate that bone marrow cells from old mutants have an intrinsic proliferation defect associated with an accelerated decline in stem cell function

♂ • however, mice show normal numbers of bone marrow cells, erythroid-committed progenitor cells, and c-Kit+, Sca-1+ and Lineage- cells at young and old ages, indicating absence of overt bone marrow cell depletion

oxidative stress ( J:217050 )

♂ • higher level of reactive oxygen species (ROS) accumulation in MEFs when cultured in both ambient oxygen (21%) and low (3%) oxygen, indicating cells are hypersensitive to oxygen

growth/size/body

decreased body weight ( J:217050 )

♂ • reduction in body weight with age

hematopoietic system

decreased hematopoietic stem cell proliferation ( J:217050 )

♂ • competitive and serial bone marrow transplantation experiments indicate that bone marrow cells from old mutants have an intrinsic proliferation defect associated with an accelerated decline in stem cell function

♂ • however, mice show normal numbers of bone marrow cells, erythroid-committed progenitor cells, and c-Kit+, Sca-1+ and Lineage- cells at young and old ages, indicating absence of overt bone marrow cell depletion

decreased B cell number ( J:217050 )

♂ • mice exhibit a decrease in the proportion of B lymphocytes with age

♂ • old (52-55 weeks) mice treated with N-acetyl cysteine long-term show normal numbers of B-cell proportions in peripheral blood

decreased T cell number ( J:217050 )

♂ • mice exhibit a decrease in the proportion of T lymphocytes with age

♂ • old (52-55 weeks) mice treated with N-acetyl cysteine long-term show normal numbers of T-cell proportions in peripheral blood

immune system

decreased B cell number ( J:217050 )

♂ • mice exhibit a decrease in the proportion of B lymphocytes with age

♂ • old (52-55 weeks) mice treated with N-acetyl cysteine long-term show normal numbers of B-cell proportions in peripheral blood

decreased T cell number ( J:217050 )

♂ • mice exhibit a decrease in the proportion of T lymphocytes with age

♂ • old (52-55 weeks) mice treated with N-acetyl cysteine long-term show normal numbers of T-cell proportions in peripheral blood

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
dyskeratosis congenita		DOID:2729	OMIM:PS127550	J:217050

Genotype
MGI:3809483

ot3

• Allelic Composition: Dkc1^tm1.1Pjma/Y
• Genetic Background: involves: 129X1/SvJ * C57BL/6 * FVB/N

cellular

abnormal DNA repair ( J:138335 )

♂ • MEFs show an increase in DNA damage foci after treatment with etoposide and more foci are localized to the telomeres

hematopoietic system

hematopoietic system phenotype ( J:138335 )

♂N • no signs of bone marrow failure unlike in patients with X-linked dyskeratosis congenita

homeostasis/metabolism

abnormal DNA repair ( J:138335 )

♂ • MEFs show an increase in DNA damage foci after treatment with etoposide and more foci are localized to the telomeres

integument

integument phenotype ( J:138335 )

♂N • no signs of nail dystrophy, skin pigmentation problems or other characteristics seen in patients with X-linked dyskeratosis congenita