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Phenotypes Associated with This Genotype
Genotype
MGI:3618363
Allelic
Composition
Cdkn1atm1Led/Cdkn1atm1Led
Gadd45atm1Ajf/Gadd45atm1Ajf
Genetic
Background
either: (involves: 129P2/OlaHsd * 129S6/SvEvTac * C57BL/6) or (involves: 129S6/SvEvTac * 129X1/SvJ * C57BL/6)
Find Mice Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation (1 available); any Cdkn1a mutation (48 available)
Gadd45atm1Ajf mutation (1 available); any Gadd45a mutation (7 available)
phenotype observed in females
phenotype observed in males
N normal phenotype
mortality/aging
• double homozygous mice begin to die after 4 months of age and the median life span of females and males is reduced to 10 and 8 months, respectively, compared to about 22 months for wild-type

cellular
• after 14 weeks of selection with L-aspartic acid, N-(phosphonoacetyl) (PALA, an assay for gene amplification) homozygous MEFs develop resistance to up to 500uM PALA unlike wild-type cells which do not develop resistance and 20-fold greater than the resistance seen in Cdkn1a single homozygous MEFs
• low passage MEFs have a plating efficiency of up to 1.4% compared to 0.005% in wild-type cells, 0.025% in Gadd45a null cells, 1.6% in Trp53 null cells, and 1.2% in Cdkn1a null cells
• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
• segmental glomerular endothelial cell proliferation is seen in older double homozygotes

immune system
• lymphoid hyperplasia is seen in the lymph nodes and spleen of 4 month old double homozygotes
• at 7-9 months of age 73% of double homozygous females are leukopenic compared to 7% of wild-type mice and 47% of Gadd45a single homozygous females
• at 7-9 months of age 53% of double homozygous females are lymphopenic compared to 7% of wild-type mice and 40% of Gadd45a single homozygous females
• at 7-9 months of age 46% of double homozygous males are lymphopenic
• 2-fold increase in IgG1 and high levels of IgG2b and IgG3 anti-double stranded DNA antibodies at 7 - 9 months of age
• 2-fold increase in IgM at 7 - 9 months of age
• the sensitivity of primary T cell activation is increased with a 3- to 10-fold leftward shift in the dose-response curve and the maximal proliferative response is about 2-fold more than in wild-type cells
• proliferation in response to cytokines is increased; however, T cell receptor independent proliferation is not increased compared to wild-type
• after 4 months of age in female and male double homozygotes the occurrence and titer of antibodies against double stranded DNA is increased compared to wild-type mice and single homozygous mice
• after 4 months of age in female and male double homozygotes the occurrence and titer of antibodies against histones is increased compared to wild-type mice and single homozygous mice
• after 4 months of age in female and male double homozygotes the occurrence and titer of antibodies against single stranded DNA is increased compared to wild-type mice and single homozygous mice
• lymphocytic infiltrates are seen in the lung and salivary glands at 4 months of age
• some glomeruli contain inflammatory cells, nuclear debris, and mesangial cell interposition, mild dilation of the proximal tubules occurs, and mild to severe dense perivascular mononuclear cell infiltrates are seen suggesting autoimmune glomerulonphritis

renal/urinary system
• segmental endothelial cell proliferation is seen in older double homozygotes
• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
• segmental glomerular endothelial cell proliferation is seen in older double homozygotes
• 220 +/- 40 mg/dl of protein is seen in the urine of double homozygous mice suggesting chronic nephropathy
• some glomeruli contain inflammatory cells, nuclear debris, and mesangial cell interposition, mild dilation of the proximal tubules occurs, and mild to severe dense perivascular mononuclear cell infiltrates are seen suggesting autoimmune glomerulonphritis
• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
• in some glomeruli
• mild dilation of the proximal tubules

homeostasis/metabolism
• 220 +/- 40 mg/dl of protein is seen in the urine of double homozygous mice suggesting chronic nephropathy

hematopoietic system
• lymphoid hyperplasia is seen in the lymph nodes and spleen of 4 month old double homozygotes
• at 7-9 months of age 73% of double homozygous females are leukopenic compared to 7% of wild-type mice and 47% of Gadd45a single homozygous females
• at 7-9 months of age 53% of double homozygous females are lymphopenic compared to 7% of wild-type mice and 40% of Gadd45a single homozygous females
• at 7-9 months of age 46% of double homozygous males are lymphopenic
• 2-fold increase in IgG1 and high levels of IgG2b and IgG3 anti-double stranded DNA antibodies at 7 - 9 months of age
• 2-fold increase in IgM at 7 - 9 months of age
• the sensitivity of primary T cell activation is increased with a 3- to 10-fold leftward shift in the dose-response curve and the maximal proliferative response is about 2-fold more than in wild-type cells
• proliferation in response to cytokines is increased; however, T cell receptor independent proliferation is not increased compared to wild-type

cardiovascular system
• segmental endothelial cell proliferation is seen in older double homozygotes


Contributing Projects:
Mouse Genome Database (MGD), Gene Expression Database (GXD), Mouse Tumor Biology (MTB), Gene Ontology (GO), MouseCyc
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last database update
11/14/2017
MGI 6.11
The Jackson Laboratory