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Phenotypes associated with this allele
Allele Symbol
Allele Name
Allele ID 		Dkc1tm1Ppp
targeted mutation 1, Pier Paolo Pandolfi
MGI:2449175
Summary 2 genotypes
Jump to Allelic Composition Genetic Background Genotype ID
ht1
 		Dkc1tm1Ppp/Dkc1+ involves: 129S1/Sv MGI:2654712
ot2
 		Dkc1tm1Ppp/Y involves: 129S1/Sv MGI:2661986


Genotype
MGI:2654712
ht1
Allelic
Composition		 Dkc1tm1Ppp/Dkc1+
Genetic
Background		 involves: 129S1/Sv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dkc1tm1Ppp mutation (0 available); any Dkc1 mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
hematopoietic system
abnormal definitive hematopoiesis ( J:81054 )
• although most phenotypic analyses were performed on G2 male hemizygotes, authors state that G1-G2 female heterozygotes display features of bone marrow failure at a lower penetrance, consistent with the observation that some human female carriers exhibit features of X-linked dyskeratosis congenita; however, no data are presented in J:81054

immune system

respiratory system

renal/urinary system

neoplasm

cellular

integument

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
dyskeratosis congenita DOID:2729 OMIM:PS127550
 J:81054




Genotype
MGI:2661986
ot2
Allelic
Composition		 Dkc1tm1Ppp/Y
Genetic
Background		 involves: 129S1/Sv
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Dkc1tm1Ppp mutation (0 available); any Dkc1 mutation (2 available)
♀ phenotype observed in females
♂ phenotype observed in males
N normal phenotype
endocrine/exocrine glands
increased pheochromocytoma incidence ( J:81054 )
• ~4% of G1-G2 male hemizygotes (17-22 months of age) develop pheochromocytomas versus 0% of wild-type mice (20-24 months of age)
increased mammary adenocarcinoma incidence ( J:81054 )
• ~4% of G1-G2 male hemizygotes (17-22 months of age) develop mammary adenocarcinomas versus 0% of wild-type mice (20-24 months of age)

hematopoietic system
decreased common myeloid progenitor cell number ( J:81054 )
• in some cases, anemic G1 and G2 male hemizygotes display a decrease in myeloid cells, as revealed in BM cytospin preparations
extramedullary hematopoiesis ( J:81054 )
• G1 male hemizygotes exhibit extramedullary hematopoieis associated with splenomegaly
anemia ( J:81054 )
• starting at 6 months of age, ~60% of G1 and G2 male hemizygotes display severe anemia
decreased bone marrow cell number ( J:81054 )
• at 8 months of age, anemic G1 and G2 male hemizygotes show a mean BM cellularity of 67.8 7.1% versus 87.3 5.7% in wild-type control mice
decreased erythroid progenitor cell number ( J:81054 )
• at 8 months of age, anemic G1 and G2 male hemizygotes show a decrease in erythroid cells (CD71 and TER119 double-positive cells), as revealed by flow cytometric analysis
• BM colony-forming assays indicate a significant reduction of erythroid colony-forming units (CFU-Es) relative to wild-type control mice
decreased hemoglobin content ( J:81054 )
• at 8 months of age, ~60% of G1 and G2 male hemizygotes exhibit a mean hemoglobin of 10.6 4 g/dl versus 15.1 1.7 g/dl in wild-type mice
thrombocytopenia ( J:81054 )
• some G1 and G2 male hemizygotes exhibit reduced platelet counts relative to wild-type control mice
decreased leukocyte cell number ( J:81054 )
• starting at 6 months of age, ~60% of G1 and G2 male hemizygotes become mildly leukopenic as a result of lymphopenia, with a mean white blood cell count of 4526 3311 per l versus 8215 3795 per l in wild-type control mice
decreased lymphocyte cell number ( J:81054 )
• starting at 6 months of age, ~60% of G1 and G2 male hemizygotes are lymphopenic with a mean absolute number of lymphocytes equal to 2428 1978 per l versus 5352 2945 per l in wild-type control mice
decreased B cell number ( J:81054 )
• at 8 months of age, some G1 and G2 male hemizygotes exhibit a specific reduction in B lymphocytes (CD3 and B220 positive cells) relative to wild-type control mice, as revealed by flow cytometric analysis
decreased pre-B cell number ( J:81054 )
• BM colony-forming assays indicate a significant reduction of pre- B colony-forming units (CFU-preBs) relative to wild-type control mice
abnormal spleen morphology ( J:81054 )
• G1-G2 male hemizygotes show total effacement of the architecture of splenic tissue, with loss of red and white pulp areas
enlarged spleen ( J:81054 )
• G1-G2 male hemizygotes exhibit splenomegaly
abnormal bone marrow cell physiology ( J:81054 )
• G1 and G2 male hemizygotes exhibit bone marrow failure prior to the onset of disease

immune system
decreased leukocyte cell number ( J:81054 )
• starting at 6 months of age, ~60% of G1 and G2 male hemizygotes become mildly leukopenic as a result of lymphopenia, with a mean white blood cell count of 4526 3311 per l versus 8215 3795 per l in wild-type control mice
decreased lymphocyte cell number ( J:81054 )
• starting at 6 months of age, ~60% of G1 and G2 male hemizygotes are lymphopenic with a mean absolute number of lymphocytes equal to 2428 1978 per l versus 5352 2945 per l in wild-type control mice
decreased B cell number ( J:81054 )
• at 8 months of age, some G1 and G2 male hemizygotes exhibit a specific reduction in B lymphocytes (CD3 and B220 positive cells) relative to wild-type control mice, as revealed by flow cytometric analysis
decreased pre-B cell number ( J:81054 )
• BM colony-forming assays indicate a significant reduction of pre- B colony-forming units (CFU-preBs) relative to wild-type control mice
abnormal spleen morphology ( J:81054 )
• G1-G2 male hemizygotes show total effacement of the architecture of splenic tissue, with loss of red and white pulp areas
enlarged spleen ( J:81054 )
• G1-G2 male hemizygotes exhibit splenomegaly
lung inflammation ( J:81054 )
• G1 male hemizygotes show inflammatory cellular infiltrates in their lungs

respiratory system
lung inflammation ( J:81054 )
• G1 male hemizygotes show inflammatory cellular infiltrates in their lungs
increased lung carcinoma incidence ( J:81054 )
• ~25% of G1-G2 male hemizygotes (17-22 months of age) develop lung carcinomas versus less than 10% of wild-type mice (20-24 months of age)
abnormal pulmonary alveolus morphology ( J:81054 )
• fusion of the alveolar spaces
increased pulmonary alveolus wall thickness ( J:81054 )
• thickening of the alveolar walls
abnormal pulmonary alveolar parenchyma morphology ( J:81054 )
• G1 male hemizygotes exhibit disruption of the normal architecture of the lung parenchyma due to fusion of the alveolar spaces and thickening of the alveolar walls

renal/urinary system
glomerulosclerosis ( J:81054 )
• G1 male hemizygotes show a significant number of atrophic proximal tubules surrounded by sclerotic glomeruli
• glomerulosclerotic tufts display solidified areas and are adjacent to normal-appearing glomeruli
renal tubule atrophy ( J:81054 )
• a significant number of atrophic proximal tubules is observed
abnormal proximal convoluted tubule morphology ( J:81054 )
• G1 male hemizygotes show a significant number of atrophic proximal tubules surrounded by sclerotic glomeruli

neoplasm
increased pheochromocytoma incidence ( J:81054 )
• ~4% of G1-G2 male hemizygotes (17-22 months of age) develop pheochromocytomas versus 0% of wild-type mice (20-24 months of age)
increased B cell derived lymphoma incidence ( J:81054 )
• ~17% of G1-G2 male hemizygotes (17-22 months of age) develop B-cell lymphomas versus less than 4% of wild-type mice (20-24 months of age)
increased malignant tumor incidence ( J:81054 )
• common tumors include lung carcinomas and adenocarcinomas of the mammary gland; one case of renal cell carcinoma is observed
• 50% of G1-G2 male hemizygotes develop malignant tumors during their life-span
increased mammary adenocarcinoma incidence ( J:81054 )
• ~4% of G1-G2 male hemizygotes (17-22 months of age) develop mammary adenocarcinomas versus 0% of wild-type mice (20-24 months of age)
increased lung carcinoma incidence ( J:81054 )
• ~25% of G1-G2 male hemizygotes (17-22 months of age) develop lung carcinomas versus less than 10% of wild-type mice (20-24 months of age)
increased fibrosarcoma incidence ( J:81054 )
• ~4% of G1-G2 male hemizygotes (17-22 months of age) develop fibrosarcomas invading the skeletal muscle versus 0% of wild-type mice (20-24 months of age)

cellular
decreased telomere length ( J:81054 )
• 30% of early G4 male hemizygotes display a reduction of telomere length in primary B lymphocytes, as determined by flow-FISH analysis
• in addition, G4 male hemizygotes show a loss of telomere repeats on individual chromosome ends, as shown by quantitative-FISH analysis
• however, no changes in telomere length or in the relative number of telomere repeats are detected prior to G4
• reduced telomere length in early G4 hemizygotes is accompanied by a 40% decrease of telomerase activity in spleen-derived primary B lymphocytes along with a 1.2-fold reduction in mouse telomerase RNA levels
abnormal cell physiology ( J:81054 )
• B lymphocytes from G1 and G2 male hemizygotes display impaired rRNA pseudouridylation and ribosome function prior to the onset of dyskeratosis congenita
increased fibroblast apoptosis ( J:81054 )
• early passage MEFs derived from G2 male hemizygotes are hypersensitive to drugs that inhibit translation, and undergo apoptosis at a significantly higher rate than wild-type MEFs

adipose tissue
increased total body fat amount ( J:81054 )
• at 8 months of age, anemic G1 and G2 male hemizygotes show decreased BM cellularity along with a relative increase in adipose and fibrous tissue

integument
increased mammary adenocarcinoma incidence ( J:81054 )
• ~4% of G1-G2 male hemizygotes (17-22 months of age) develop mammary adenocarcinomas versus 0% of wild-type mice (20-24 months of age)
abnormal epidermis stratum granulosum morphology ( J:81054 )
• 7 of 25 G1 male hemizygotes display an enlarged granular layer, as identified with anti-filaggrin antibody
abnormal epidermis stratum spinosum morphology ( J:81054 )
• 7 of 25 G1 male hemizygotes show an expansion of the spinal layer with keratinocytes showing prominent nuclei
epidermal hyperplasia ( J:81054 )
• 7 of 25 G1 male hemizygotes epidermal hyperplastic changes due to an expansion of the nucleated cell layers
dyskeratosis ( J:81054 )
• 7 of 25 G1 male hemizygotes display dyskeratosis of the skin

growth/size/body
enlarged spleen ( J:81054 )
• G1-G2 male hemizygotes exhibit splenomegaly

Mouse Models of Human Disease
 DO ID OMIM ID(s) Ref(s)
dyskeratosis congenita DOID:2729 OMIM:PS127550
 J:81054




Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Models of Human Cancer database (MMHCdb) (formerly Mouse Tumor Biology (MTB)), Gene Ontology (GO)
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12/17/2024
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