All Phenotypes Dkc1<tm1Ppp> MGI Mouse

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

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 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)

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

abnormal pulmonary alveolus wall morphology ( 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 )

• 50% of G1-G2 male hemizygotes develop malignant tumors during their life-span

• common tumors include lung carcinomas and adenocarcinomas of the mammary gland; one case of renal cell carcinoma is observed

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

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

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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