Phenotypes associated with this allele

• Allele Symbol: Arhgap1^tm1Yizh
• Allele Name: targeted mutation 1, Yi Zheng
• Allele ID: MGI:3606252
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Arhgap1^tm1Yizh/Arhgap1^tm1Yizh	involves: 129S6/SvEvTac	MGI:3606423
hm2	Arhgap1^tm1Yizh/Arhgap1^tm1Yizh	involves: 129S6/SvEvTac * C57BL/6	MGI:3762613
cx3	Arhgap1^tm1Yizh/Arhgap1^tm1Yizh Trp53^tm1Tyj/Trp53^+	involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6	MGI:3762617

Genotype
MGI:3606423

hm1

• Allelic Composition: Arhgap1^tm1Yizh/Arhgap1^tm1Yizh
• Genetic Background: involves: 129S6/SvEvTac

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

mortality/aging

postnatal lethality ( J:101418 )

• about 93% of pups die before weaning

growth/size/body

decreased embryo size ( J:101418 )

• embryos are 25-40% smaller

postnatal growth retardation ( J:101418 )

• prior to weaning pups are 25-40% smaller than wild-type and those that survive past weaning are about 30% smaller but are fertile

cellular

abnormal cell morphology ( J:101418 )

• primary MEFs display robust spontaneous filopodia and actin microspikes

increased apoptosis ( J:101418 )

• increased apoptosis is seen in the embryonic liver and brain; however cell proliferation and cell cycle are normal

increased fibroblast apoptosis ( J:101418 )

• increased apoptosis is seen in primary MEFs

increased neuron apoptosis ( J:101418 )

• at E14.5, E15.5 and E18.5, apoptosis is increased but proliferation is normal

nervous system

increased neuron apoptosis ( J:101418 )

• at E14.5, E15.5 and E18.5, apoptosis is increased but proliferation is normal

immune system

thymus hypoplasia ( J:101418 )

• thymus cell number but not cell size is decreased

spleen hypoplasia ( J:101418 )

• spleen cell number but not cell size is decreased

liver/biliary system

liver hypoplasia ( J:101418 )

• liver cell number but not cell size is decreased and apoptosis is increased but proliferation is normal at E14.5, E15.5 and E18.5

embryo

decreased embryo size ( J:101418 )

• embryos are 25-40% smaller

hematopoietic system

thymus hypoplasia ( J:101418 )

• thymus cell number but not cell size is decreased

spleen hypoplasia ( J:101418 )

• spleen cell number but not cell size is decreased

endocrine/exocrine glands

thymus hypoplasia ( J:101418 )

• thymus cell number but not cell size is decreased

Genotype
MGI:3762613

hm2

• Allelic Composition: Arhgap1^tm1Yizh/Arhgap1^tm1Yizh
• Genetic Background: involves: 129S6/SvEvTac * C57BL/6

Reduced size and severe lordokyphosis in Arhgap1^tm1Yizh/Arhgap1^tm1Yizh mice

mortality/aging

premature death ( J:119516 )

• median life span of mutants surviving the neonatal period is 12 months compared to 27 months for wild-type

neonatal lethality, incomplete penetrance ( J:119516 )

• majority of mutants die during the neonatal period, however about 7% survive when placed under foster care

premature aging ( J:119516 )

• premature aging like phenotypes, including reduction in body mass, loss of subdermal adipose tissue, severe lordokyphosis, muscle atrophy, osteoporosis, and reduction of reepithelialization ability in wound-healing

limbs/digits/tail

decreased femur compact bone thickness ( J:119516 )

• the femurs of 8 month old mutants show reduced cortical bone thickness

homeostasis/metabolism

impaired DNA repair ( J:119516 )

• MEFs display dampened DNA damage repair activity after DNA-damaging agent treatment (H2O2, ionizing radiation, camptothecin, methyl-methane sulfonate, or mitomycin C)

impaired wound healing ( J:119516 )

• ability to tolerate stress, such as wound healing, is significantly reduced compared with wild-type; wounds show little reepithelialization in the wound edge

skeleton

decreased femur compact bone thickness ( J:119516 )

• the femurs of 8 month old mutants show reduced cortical bone thickness

kyphosis ( J:119516 )

• kyphosis becomes evident at 12 months of age

lordokyphosis ( J:119516 )

• at 15 months of age, show severe lordokyphosis

abnormal vertebral body morphology ( J:119516 )

• vertebral body exhibits a thinner, bowed cortex and thinner trabeculae at 8 months of age compared with wild-type

decreased bone mineral density ( J:119516 )

• 3-fold reduction of bone mineral density in the tibia at 15 months of age

decreased bone mineral density of femur ( J:119516 )

• 2.6-fold reduction of bone mineral density in the femur at 15 months of age

osteoporosis ( J:119516 )

• develop osteoporosis earlier than wild-type

muscle

muscular atrophy ( J:119516 )

• loss in muscle mass and muscle atrophy at 12 months of age

adipose tissue

absent subcutaneous adipose tissue ( J:119516 )

• almost complete absence of subcutaneous adipose cells in 9-month old mutants

cellular

abnormal chromosome morphology ( J:119516 )

• MEFs exhibit a variety of chromosomal aberrations, including chromatid break, premature sister chromatid separations, translocation, chromosome breaks, dicentric chromosomes and chromosome fragmentation

decreased fibroblast proliferation ( J:119516 )

• MEFs display reduced population doubling and accumulate genomic abnormalities

impaired DNA repair ( J:119516 )

• MEFs display dampened DNA damage repair activity after DNA-damaging agent treatment (H2O2, ionizing radiation, camptothecin, methyl-methane sulfonate, or mitomycin C)

growth/size/body

decreased body weight ( J:119516 )

• mutants surviving the neonatal period begin to show decelerated weight gain at 3 months of age compared with 5 months of age for wild-type

• mature mutants exhibit a 30% reduction in body weight due to a decrease in overall cellularity

hematopoietic system

abnormal hematopoietic system morphology/development ( J:119516 )

• early aging in the hematopoietic system

anemia ( J:119516 )

• develop anemia

decreased bone marrow cell number ( J:119516 )

• reduced bone marrow cellularity

abnormal hematopoietic stem cell morphology ( J:119516 )

• defects of hematopoietic stem cell engraftment to the bone marrow, with an increase in sensitivity of hematopoietic stem cells to induced mobilization

spleen hypoplasia ( J:119516 )

• spleen is reduced in mass due to a decrease in overall cellularity

decreased spleen white pulp amount ( J:119516 )

• T and B cell containing white pulp regions are reduced in 12 month old mutants

immune system

spleen hypoplasia ( J:119516 )

• spleen is reduced in mass due to a decrease in overall cellularity

decreased spleen white pulp amount ( J:119516 )

• T and B cell containing white pulp regions are reduced in 12 month old mutants

liver/biliary system

liver hypoplasia ( J:119516 )

• liver is reduced in mass due to a decrease in overall cellularity

renal/urinary system

renal hypoplasia ( J:119516 )

• kidney is reduced in mass due to a decrease in overall cellularity

reproductive system

reduced fertility ( J:119516 )

• both males and females lose fertility at an earlier age compared with wild-type, indicating a shortened fertility period

integument

absent subcutaneous adipose tissue ( J:119516 )

• almost complete absence of subcutaneous adipose cells in 9-month old mutants

abnormal hair growth ( J:119516 )

• mutants show a reduction in hair regeneration after removal of the dorsal hair by shaving compared to wild-type

Genotype
MGI:3762617

cx3

• Allelic Composition: Arhgap1^tm1Yizh/Arhgap1^tm1Yizh; Trp53^tm1Tyj/Trp53⁺
• Genetic Background: involves: 129S2/SvPas * 129S6/SvEvTac * C57BL/6

cellular

cellular phenotype ( J:119516 )

N • MEFs grow at a rate between that of heterozygous Trp53 MEFs and wild-type cells, indicating that the senescence seen in homozygous Arhgap1 mutant MEFs is rescued