Phenotypes associated with this allele
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
|
|
|
mortality/aging
|
|
• homozygous mice begin to die after 7 months of age
|
cellular
|
|
• after 20 weeks of selection with L-aspartic acid, N-(phosphonoacetyl) (PALA, an assay for gene amplification) homozygous MEFs develop resistance to up to 25uM PALA unlike wild-type cells which do not develop resistance
|
|
|
• ionizing radiation does not induce a strong G1 delay unlike in wild-type or Gadd45a null cells
|
|
|
• proliferation in response to cytokines is increased compared to wild-type; however proliferation in response to anti-CD3 is not
|
|
|
• low passage MEFs have a plating efficiency of about 1.2% compared to 0.005% in wild-type cells, 0.025% in Gadd45a null cells, 1.6% in Trp53 null cells, and up to 1.4% in Gadd45a Cdkn1a double null cells
|
immune system
|
|
• proliferation in response to cytokines is increased compared to wild-type; however proliferation in response to anti-CD3 is not
|
|
|
• after 7 months of age in female homozygotes the occurrence and titer of antibodies against double stranded DNA is increased compared to wild-type mice
|
|
|
• after 7 months of age in female homozygotes the occurrence and titer of antibodies against histones is increased compared to wild-type mice
|
|
|
• after 7 months of age in female homozygotes the occurrence and titer of antibodies against single stranded DNA is increased compared to wild-type mice
|
hematopoietic system
|
|
• proliferation in response to cytokines is increased compared to wild-type; however proliferation in response to anti-CD3 is not
|
integument
|
|
• the proportion of awl and auchene hairs are increased relative to in wild-type mice but not as much as in heterozygous mice
|
|
|
• the proportion of awl and auchene hairs are increased relative to in wild-type mice but not as much as in heterozygous mice
|
|
|
• the proportion of zigzag hair is reduced relative to in wild-type mice but not as much as in heterozygous mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
|
|
|
cellular
|
|
• MEFs are deficient in their ability to arrest in G1 in response to DNA damage and nucleotide pool perturbation
• however, no gross abnormalities are seen in animals observed to 7 months of age
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
|
|
|
neoplasm
|
|
• no difference in the overall rate or frequency of ENU induced tumorigenesis is found however homozygotes have an increased incidence of sarcomas and liver tumors and a decreased incidence of lymphomas
|
|
|
• a two fold increase in the apoptotic index in lymphomas from homozygotes relative to wild-types is seen
|
Allelic
Composition |
Cdkn1atm1Led/Cdkn1a+
|
|
Genetic
Background |
involves: 129S6/SvEvTac |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
|
|
|
integument
|
|
• the proportion of awl and auchene hairs are increased relative to in wild-type mice
|
|
|
• the proportion of awl and auchene hairs are increased relative to in wild-type mice
|
|
|
• the proportion of zigzag hair is reduced relative to in wild-type mice
|
hematopoietic system
|
|
• when Cdkn1ctm2.1Kei is inherited maternally, hematopoietic stem (KSL) cells from pIpC-treated mice exhibit reduced colony formation in vitro before and after coculture with OP9 cells compared with control cells
|
immune system
|
|
• double negative to double positive differentiation is blocked unlike in wild-type mice
|
hematopoietic system
|
|
• double negative to double positive differentiation is blocked unlike in wild-type mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
Ctnnb1tm1Mmt mutation
(0 available);
any
Ctnnb1 mutation
(49 available)
Tg(Upk2-cre)6Xrw mutation
(0 available)
|
|
|
mortality/aging
|
|
• mean survival of 237 days and median survival of 238 days
|
neoplasm
|
|
• mice rapidly develop urothelial cell carcinoma
|
renal/urinary system
|
|
• mice rapidly develop urothelial cell carcinoma
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
Tg(Upk2-cre)6Xrw mutation
(0 available)
|
|
|
neoplasm
|
N |
• mice do not develop urothelial tumors or other urothelial abnormalities
|
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
|
|
|
• global mesangial proliferation involving 10 - 100% of glomeruli is seen in older double homozygotes
|
|
|
• proliferation in response to cytokines is increased; however, T cell receptor independent proliferation is not increased compared to wild-type
|
|
|
• 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
|
|
|
• 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
|
|
|
• mild dilation of the proximal tubules
|
homeostasis/metabolism
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
|
Allelic
Composition |
Ccne1tm1Jro/?
Cdkn1atm1Led/Cdkn1atm1Led
|
|
Genetic
Background |
either: (involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6J) or (involves: 129S4/SvJaeSor * 129S6/SvEvTac * C57BL/6 * C57BL/6J) |
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Ccne1tm1Jro mutation
(0 available);
any
Ccne1 mutation
(23 available)
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
|
|
|
cellular
|
|
• during a 3T3 immortalization protocol double mutant MEFs display grossly altered cell morphology unlike MEFs homozygous null for Cdkn1a alone
|
|
|
• cell proliferation in double mutant MEFs is reduced compared to MEFs homozygous null for Cdkn1a alone
|
|
|
• double mutant MEFs have more cells that are tetraploid in early passages and aneuploid in later passages compared to MEFs homozygous null for Cdkn1a alone
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
Wrntm1Led mutation
(0 available);
any
Wrn mutation
(91 available)
|
|
|
neoplasm
|
|
• 56% of mice older than 15 months developed hyperplasias or tumors
• no acceleration of tumorigenesis, in comparison to Wrntm1Led homozygous mice
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
Kdm8tm1.2Tasu mutation
(0 available);
any
Kdm8 mutation
(17 available)
|
|
|
mortality/aging
embryo
|
|
• avascular yolk sacs at E10.5
|
|
|
• severely growth retarded at E10.5
• however, embryos are slightly larger than littermates homozygous for Jmjd5tm1.2Tasu alone
|
cardiovascular system
|
|
• avascular yolk sacs at E10.5
|
growth/size/body
|
|
• severely growth retarded at E10.5
• however, embryos are slightly larger than littermates homozygous for Jmjd5tm1.2Tasu alone
|
cellular
|
|
• senescence-like G1 cell cycle arrest
|
|
|
• senescence-like G1 cell cycle arrest
|
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
Hus1tm1Led mutation
(0 available);
any
Hus1 mutation
(20 available)
|
|
|
cellular
|
|
• double homozygous MEFs are 5- to 10-fold more sensitive to hydroxyurea compared to cells null for Cdkn1a only
|
|
|
• double homozygous MEFs are more sensitive to UV but not to ionizing radiation compared to cells null for Cdkn1a only
|
|
|
• mutant MEFs display increased numbers of chromosomal abnormalities; however unlike MEFs from Hus1 single homozygotes cells from 3 of 13 double homozygotes proliferated in culture
|
mortality/aging
|
|
• improved embryonic survival
• death within 24 hours of birth
|
mortality/aging
|
|
• normal numbers at E16.5
• 65% die before birth
|
|
|
• no live births when Cdkn1ctm1Sje is maternally inherited
|
growth/size/body
digestive/alimentary system
muscle
|
|
• fewer and shorter myotubes in the hind limb
• nuclei in myotubes larger and abnormal in shape
• increased apoptosis
|
|
|
• severely reduced in size
• thinner
|
|
|
• reduced intercostals muscles
• reduced head muscles
• body wall musculature severely reduced
|
respiratory system
|
|
• distal air sacs fail to differentiate
• primitive alveoli do not develop
|
|
|
• luminal space is reduced
|
|
|
• luminal space is reduced
|
craniofacial
renal/urinary system
skeleton
|
|
• ribs join the sternum at a wider than normal angle (90o)
|
|
|
• 9th rib usually
• sometimes also the 7th rib
|
vision/eye
limbs/digits/tail
|
|
| Find Mice |
Using the International Mouse Strain Resource (IMSR)
Mouse lines carrying:
Cdkn1atm1Led mutation
(1 available);
any
Cdkn1a mutation
(60 available)
Fgfr3tm1Cxd mutation
(0 available);
any
Fgfr3 mutation
(52 available)
|
|
|
growth/size/body
skeleton
|
|
• length of all bones formed by endochondral ossification is shorter than in controls but no different from single homozygous Fgfr3tm1Cdx mutants
|
|
|
• exhibit similar growth plate defects as single homozygous Fgfr3tm1Cxd mutant mice
|
Analysis Tools