Phenotypes for Dkc1 MGI:2661986 MGI Mouse

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)

abnormal definitive hematopoiesis ( J:81054 )

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

decreased spleen red pulp amount ( J:81054 )

decreased spleen white pulp amount ( J:81054 )

abnormal bone marrow cell physiology ( J:81054 )

• G1 and G2 male hemizygotes exhibit bone marrow failure prior to the onset of disease

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

decreased spleen red pulp amount ( J:81054 )

decreased spleen white pulp amount ( J:81054 )

lung inflammation ( J:81054 )

• G1 male hemizygotes show inflammatory cellular infiltrates in their lungs

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)

pulmonary interstitial fibrosis ( J:81054 )

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

increased renal carcinoma incidence ( J:81054 )

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

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 renal carcinoma incidence ( J:81054 )

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)

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

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

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

enlarged spleen ( J:81054 )

• G1-G2 male hemizygotes exhibit splenomegaly

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

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)
Citing These Resources Funding Information Warranty Disclaimer, Privacy Notice, Licensing, & Copyright Send questions and comments to User Support.	last database update 12/17/2024 MGI 6.24