Phenotypes associated with this allele

• Allele Symbol: Pot1a^tm1Schg
• Allele Name: targeted mutation 1, Sandy Chang
• Allele ID: MGI:3665306
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Pot1a^tm1Schg/Pot1a^tm1.1Schg	involves: 129S7/SvEvBrd * C57BL/6	MGI:3690104
cx2	Pot1a^tm1Schg/Pot1a^tm1.1Schg Trp53^tm1Tyj/Trp53^tm1Tyj	involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6	MGI:3690106

Genotype
MGI:3690104

ht1

• Allelic Composition: Pot1a^tm1Schg/Pot1a^tm1.1Schg
• Genetic Background: involves: 129S7/SvEvBrd * C57BL/6

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

cellular

abnormal chromosome morphology ( J:112184 )

• 24 hours following AdCre treatment, 31% and 24% of cells contain at least 4 foci positive for markers of DNA damage (53BP1, gammaH2AX, respectively)

• 96 hours after treatment, 50% of MEFs show at least six telomere-dysfunction induced foci (TIFs), indicating robust induction of DNA damage response at the telomeres, without induction of p53-dependent apoptosis

• ~73% of MEFs treated with cre display naked telomere ends

abnormal telomere length ( J:112184 )

• telomere elongation that occurs in absence of Pot1a results in a 2-fold increase in length of G strand overhang at telomeres in MEFs treated with cre

decreased cell proliferation ( J:112184 )

• after adenoviral cre (AdCre) treatment, cultured mouse embryonic fibroblasts (MEFs) show significant impairment of proliferation while little effect is seen in mutant MEFs treated with control vector

• this correlates to an 11-fold increase in number of cells expressing senescence-associated proteins and a ~4-fold decrease in BrdU-positive cells

Genotype
MGI:3690106

cx2

• Allelic Composition: Pot1a^tm1Schg/Pot1a^tm1.1Schg; Trp53^tm1Tyj/Trp53^tm1Tyj
• Genetic Background: involves: 129S2/SvPas * 129S7/SvEvBrd * C57BL/6

cellular

cellular phenotype ( J:112184 )

N • in double null MEFs, senescence-like growth arrest is not observed like in p53-intact, Pot1a-null MEFs

abnormal chromosome morphology ( J:112184 )

• extrachromosomal telomeric signals are detected in metaphase spreads of all treated MEF lines

• after cre treatment, all mutant MEF lines display multiple chromosome aberrations, including anaphase bridges (16% of cells), chromosomal fusions, breaks, and fragments 35/103 metaphases); in contrast, no anaphase bridges and minimal chromosome aberrations (4/135 metaphases) are observed in control MEFs

• a progressive increase in number of fused chromosomes is seen in all mutant metaphases examined 48-96 hours after cre treatment of MEFs

abnormal cell physiology ( J:112184 )

• cre-treated MEFs display chromosomal instability and form 8-fold more transformed foci compared to control cells

• 4/4 subclones form soft tissue sarcomas following subcutaneous injection into SCID mice

elevated level of mitotic sister chromatid exchange ( J:112184 )

• in cre-treated MEFs, a 4-fold increase in both lagging and leading-strand telomeric-sister chromatid exchange (T-SCE) is observed compared to control virus treated MEFs (Pot1a-sufficient); genomic SCE is not observed above background levels in treated cells

chromosome breakage ( J:112184 )

• chromosome breaks and fragments are found in a significant number of metaphase spreads assayed by telomere PNA-FISH