Phenotypes associated with this allele

• Allele Symbol: Rae1⁺
• Allele Name: wild type
• Allele ID: MGI:2440370
• Summary: 4 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
ht1	Rae1^tm1Jvd/Rae1^+	Not Specified	MGI:3620037
cx2	Nup88^em1Jvd/Nup88^+ Nup98^tm1Jvd/Nup98^+ Rae1^tm1Jvd/Rae1^+	involves: C57BL/6	MGI:6377639
cx3	Bub3^tm1Jvd/Bub3^+ Rae1^tm1Jvd/Rae1^+	Not Specified	MGI:3620038
cx4	Nup98^tm1Jvd/Nup98^+ Rae1^tm1Jvd/Rae1^+	Not Specified	MGI:6377636

Genotype
MGI:3620037

ht1

• Allelic Composition: Rae1^tm1Jvd/Rae1⁺
• Genetic Background: Not Specified

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

cellular

aneuploidy ( J:81546 , J:105717 )

• in heterozygous MEFs after 5 passages about 20% of metaphases are aneuploid compared to about 9% in wild-type cells and a wider range of nonmodal chromosome numbers is seen (J:81546)

• at 5 months of age, 9% of splenocytes are aneuploid (J:81546)

• the number of aneuploid splenocytes increases from 9% at 5 months to 33% at 24 months compared to only 3% in wild-type mice at 35 months (J:105717)

abnormal cell cycle checkpoint function ( J:81546 , J:105717 )

• after 12 hours of treatment with 200 ng/ml nocodazole (induces spindle damage) only 2.5% of heterozygous MEFs are arrested compared to 15% of wild-type cells and after 4 hours in serum without nocodazole (recovery phase) more cells are present with 4N DNA content suggesting progression to G1 without cell division (J:81546)

• overexpression of Rae1 can rescue the mitotic checkpoint defect (J:81546)

• after nocodazole treatment the time for 50% of cells to exit prometaphase arrest is reduced to 3 hours compared to 7.2 hours for wild-type MEFs (J:105717)

abnormal mitosis ( J:81546 , J:105717 )

• lagging chromosomes are seen in 5% of anaphase figures compared to 2% of wild-type figures (J:81546)

• in splenocytes prematurely separated sister chromatids increase from 0 at 5 months to being present in 10-11% of metaphases at 24-27 months compared to 0 at 27 months and only 4% at 35 months in wild-type (J:105717)

• however, no chromosome breaks or fusions are seen at 24 months of age (J:105717)

neoplasm

increased incidence of tumors by chemical induction ( J:81546 )

• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in heterozygotes compared to wild-type mice

• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:81546 )

• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in heterozygotes compared to wild-type mice

• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice

Genotype
MGI:6377639

cx2

• Allelic Composition: Nup88^em1Jvd/Nup88⁺; Nup98^tm1Jvd/Nup98⁺; Rae1^tm1Jvd/Rae1⁺
• Genetic Background: involves: C57BL/6

cellular

abnormal mitosis ( J:231166 )

• chromosome segregation errors are reduced to 18% from 37% in double Rae1^tm1Jvd Nup98^tm1Jvd heterozygotes and the mitotic checkpoint is fully restored

Genotype
MGI:3620038

cx3

• Allelic Composition: Bub3^tm1Jvd/Bub3⁺; Rae1^tm1Jvd/Rae1⁺
• Genetic Background: Not Specified

Reduced lifespan, cataract, lordokyphosis and cachexia in Bub3^tm1Jvd/Bub3⁺ Rae1^tm1Jvd/Rae1⁺ mice

mortality/aging

premature aging ( J:105717 )

• seen in the second year of life

cellular

aneuploidy ( J:81546 , J:105717 )

• in double heterozygous MEFs after 5 passages aneuploid cells are increased by 32% compared to wild-type cells and a wider range of nonmodal chromosome numbers is seen compared to single heterozygous or wild-type MEFs (J:81546)

• at 5 months of age, 37% of splenocytes are aneuploid compared to 9% in single heterozygotes (J:81546)

• the number of aneuploid splenocytes increases from 37% at 5 months to 47% at 24 months compared to only 3% in wild-type mice at 35 months (J:105717)

abnormal cell cycle checkpoint function ( J:105717 )

• after nocodazole treatment the time for 50% of cells to exit prometaphase arrest is reduced to 2.2 hours compared to 7.2 hours for wild-type MEFs

abnormal mitosis ( J:81546 , J:105717 )

• prematurely separated sister chromatids are seen in 19% and 13% of mitotic figures from MEFs and splenocytes (at 5 months of age), respectively (J:81546)

• lagging chromosomes are seen in 15% of anaphase figures compared to 5% of single heterozygous and 2% of wild-type figures (J:81546)

• in splenocytes prematurely separated sister chromatids increase from 14% at 5 months to being present in 24% of metaphases at 24 months compared to 0 at 27 months and only 4% at 35 months in wild-type (J:105717)

• however, no chromosome breaks or fusions are seen at 24 months of age (J:105717)

• 47% of anaphases have multiple lagging chromosomes compared to 0% in wild-type MEFs (J:105717)

decreased cell proliferation ( J:81546 )

• double heterozygous MEFs grow slower than single heterozygous or wild-type MEFs

abnormal cellular replicative senescence ( J:105717 )

• at passage 5 and 7 increased expression of senescence related genes in MEFs is seen

• at passage 7 but not passage 3, double heterozygous MEFs grow slower than single heterozygous or wild-type MEFs

adipose tissue

decreased subcutaneous adipose tissue amount ( J:105717 )

• decreased thickness of the subcutaneous adipose tissue

decreased total body fat amount ( J:105717 )

• at 27 months of age a dramatic decrease in body fat is seen

growth/size/body

weight loss ( J:105717 )

• body weight is similar to wild-type at 5 months of age but significantly lower by 24 months of age

cachexia ( J:105717 )

muscle

muscle degeneration ( J:105717 )

• clear signs of skeletal muscle degeneration and atrophy are seen in mice with lordokyphosis

muscular atrophy ( J:105717 )

• clear signs of skeletal muscle degeneration and atrophy are seen in mice with lordokyphosis

skeleton

lordokyphosis ( J:105717 )

• lordokyphosis is seen at an earlier age and with increased severity compared to single heterozygous or wild-type mice

vision/eye

cataract ( J:105717 )

• incidence of cataract formation is increased and the latency is decreased compared to single heterozygotes

neoplasm

increased incidence of tumors by chemical induction ( J:81546 )

• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in double heterozygotes compared to wild-type mice

• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice

homeostasis/metabolism

increased incidence of tumors by chemical induction ( J:81546 )

• a single application of 50 ul of 0.5% DMBA at P5 results in an increased incidence of lung tumors and more tumors per animal in double heterozygotes compared to wild-type mice

• however, no difference in spontaneous tumor incidence is seen compared to wild-type mice

integument

decreased subcutaneous adipose tissue amount ( J:105717 )

• decreased thickness of the subcutaneous adipose tissue

thin dermal layer ( J:105717 )

• from 5 to 27 months of age dermal thickness decreases by 21% lower compared a decrease of 9% in wild-type mice

Genotype
MGI:6377636

cx4

• Allelic Composition: Nup98^tm1Jvd/Nup98⁺; Rae1^tm1Jvd/Rae1⁺
• Genetic Background: Not Specified

cellular

abnormal cell cycle checkpoint function ( J:231166 )

• MEFs exhibit mitotic checkpoint defects

abnormal mitosis ( J:231166 )

• MEFs have increased rates of chromatin bridges and lagging chromosomes indicating chromosome segregation errors

• incomplete centrosome separation is increased in MEFs

• MEFs treated with the PLK1 inhibitor BI2536 show restoration of normal centrosome separation

abnormal mitotic spindle morphology ( J:231166 )

• MEFs exhibit more frequent spindle geometry defects showing mitotic spindle asymmetry