Phenotypes associated with this allele

• Allele Symbol: Cdkn1b^tm1Jro
• Allele Name: targeted mutation 1, James M Roberts
• Allele ID: MGI:2387694
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Cdkn1b^tm1Jro/Cdkn1b^tm1Jro	involves: 129S4/SvJaeSor * C57BL/6	MGI:3842938
cn2	Cdkn1b^tm1Jro/Cdkn1b^tm1Jro Rb1^tm3Tyj/Rb1^tm3Tyj Trp53^tm1Brn/Trp53^tm1Brn Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0	involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N	MGI:7484794

Genotype
MGI:3842938

hm1

• Allelic Composition: Cdkn1b^tm1Jro/Cdkn1b^tm1Jro
• Genetic Background: involves: 129S4/SvJaeSor * C57BL/6

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

cellular

decreased cell proliferation ( J:71780 )

• modest decrease in cell proliferation in MEFs

decreased T cell proliferation ( J:71780 )

• in response to stimulation with anti-TCR antibodies

• addition of exogenous IL2 partially restores proliferation

decreased keratinocyte proliferation ( J:71780 )

• keratinocytes at the edge of a punch wound display decreased proliferation

hematopoietic system

decreased T cell proliferation ( J:71780 )

• in response to stimulation with anti-TCR antibodies

• addition of exogenous IL2 partially restores proliferation

homeostasis/metabolism

delayed wound healing ( J:71780 )

• closure of full thickness punch wounds is delayed suggesting a defect in keratinocyte proliferation

• no difference is detected in the rate of closure of incision wounds

growth/size/body

increased body weight ( J:71780 )

immune system

decreased T cell proliferation ( J:71780 )

• in response to stimulation with anti-TCR antibodies

• addition of exogenous IL2 partially restores proliferation

integument

decreased keratinocyte proliferation ( J:71780 )

• keratinocytes at the edge of a punch wound display decreased proliferation

Genotype
MGI:7484794

cn2

• Allelic Composition: Cdkn1b^tm1Jro/Cdkn1b^tm1Jro; Rb1^tm3Tyj/Rb1^tm3Tyj; Trp53^tm1Brn/Trp53^tm1Brn; Tg(Sp7-tTA,tetO-EGFP/cre)1Amc/0
• Genetic Background: involves: 129P2/OlaHsd * 129S4/SvJae * C57BL/6J * CD-1 * FVB/N

mortality/aging

increased tumor-free survival time ( J:318035 )

• overall survival is significantly longer than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, regardless of whether tumors are located in the jaw or limbs

neoplasm

abnormal tumor pathology ( J:318035 )

• osteosarcoma tumors exhibit a marked increase in mutant p27^T187A levels while tumor lysates show elevated CDKN1B (p27) protein levels with similar SKP2 expression relative to tumors from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

• treatment of early passage tumor cells with CHX (a protein synthesis inhibitor) and MG132 (a proteasome inhibitor) showed enhanced stability of the mutant p27^T187A protein, with no significant change in Cdkn1b (p27) mRNA levels

• TUNEL and cleaved caspase-3 immunostaining showed increased apoptosis, while flow cytometry using annexin V/7-AAD staining showed a significant increase in the early apoptotic population

• primary osteosarcoma tumor cells exhibit less sphere-forming capacity and show reduced stem-like properties (such as ALDH activity) and lower stem-cell frequency and self-renewal ability than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

decreased tumor growth/size ( J:318035 )

• both limb and jaw osteosarcoma tumors are significantly smaller than those from age-matched mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, indicating delayed tumor progression

• in vivo, tumor growth rate is significantly slower than that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

• in vitro, primary osteosarcoma cells grown in monolayer cultures proliferate significantly less than tumor cells from mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele

increased osteosarcoma incidence ( J:318035 )

• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age

• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)

skeleton

increased osteosarcoma incidence ( J:318035 )

• mice develop osteosarcomas with 100% penetrance at an average of 169 +/- 43.69 days of age

• anatomic distribution of tumors is very similar to that of mutant mice that are homozygous for the wild-type Cdkn1b (p27) allele, including the head and jaw (40.7% versus 42.9%), limbs (39% versus 38.8%), spine and sacrum (10.2% versus 8.2%), and trunk (10.2% versus 10.2%)

growth/size/body

growth/size/body region phenotype ( J:318035 )

N • mice show no evidence of delayed or stunted growth

reproductive system

reproductive system phenotype ( J:318035 )

N • mice are fertile