Phenotypes associated with this allele

• Allele Symbol: Pgap4^em1Osbir
• Allele Name: endonuclease-mediated mutation 1, Taroh Kinoshita
• Allele ID: MGI:6471949
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Pgap4^em1Osbir/Pgap4^em1Osbir	involves: C57BL/6NSlc	MGI:7539049

Genotype
MGI:7539049

hm1

• Allelic Composition: Pgap4^em1Osbir/Pgap4^em1Osbir
• Genetic Background: involves: C57BL/6NSlc

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

homeostasis/metabolism

increased circulating calcium level ( J:333707 )

• blood calcium level is significantly higher than in wild-type controls

increased circulating alkaline phosphatase level ( J:333707 )

• blood alkaline phosphatase level (ALP) levels are ~3 times higher than in wild-type controls, suggesting that the cell surface level of ALP is reduced

skeleton

short tibia ( J:333707 )

♀ • females show a significantly shorter tibia length (mm) than wild-type controls

abnormal rib morphology ( J:333707 )

♂ • 42.9% of males exhibit bowed ribs

abnormal thoracic cage shape ( J:333707 )

♂ • 42.9% of males exhibit a caved-in ribcage

abnormal cervical vertebrae morphology ( J:333707 )

♂ • 57.1% of males show abnormally shaped cervical vertebrae

♂ • however, % of males with a deformed ventral tubercle of atlas is equivalent to that in wild-type controls (14.3%)

abnormal ventral tubercle of atlas morphology ( J:333707 )

♀ • 57.1% of females show a deformed ventral tubercle of atlas relative to 14.3% in wild-type controls

abnormal bone structure ( J:333707 )

♂ • males exhibit a significantly smaller bone area (cm2) than wild-type controls

decreased bone mineral content ( J:333707 )

• bone mineral content (g) is significantly lower than in wild-type controls

abnormal bone ossification ( J:333707 )

decreased bone mineralization ( J:333707 )

behavior/neurological

impaired contextual conditioning behavior ( J:333707 )

• in a contextual fear conditioning test, mice show a lower % of freezing time at each time point analyzed, suggesting impaired memory formation

abnormal response to novel object ( J:333707 )

• in a sociability test, mice spend more time in front of the cage near an unstimulating novel object than wild-type controls

• however, time spent near a stranger mouse is comparable to that in wild-type controls

decreased locomotor activity ( J:333707 )

• in the open field test, the distance traveled is decreased, particularly in the periphery of the field, while the average speed is significantly reduced, indicating reduced locomotion activity

• average home cage activity is significantly lower than that in wild-type controls in the dark, but not in the light, state

• however, the % of time spent in the center region and latency to center entry in the open field are normal, suggesting lack of anxiety-like behaviors

immune system

increased Ly6C-positive immature NK cell number ( J:333707 )

♀ • females show a slight increase in CD11b- Ly6C+ NK cells

increased susceptibility to infection induced morbidity/mortality ( J:333707 )

• after intracerebral inoculation with pathogenic PrP^Sc strains (Fukuoka-1 or Chandler), mice die significantly earlier than similarly inoculated wild-type controls, with an average survival of less than 150 days post inoculation (dpi)

increased susceptibility to prion infection ( J:333707 )

• after intracerebral inoculation with Fukuoka-1 (a mouse-adapted Gerstmann-Straussler-Scheinker syndrome prion strain) or Chandler (a mouse-adapted scrapie prion strain), mice exhibit a significantly shorter incubation period but no differences in PrP^Sc accumulation or levels of gliosis in deceased (endpoint) brains relative to similarly inoculated wild-type controls

• at 50 days dpi with the Fukuoka-1 strain, PrP^Sc accumulation is robustly increased relative to wild-type controls, indicating accelerated conversion of PrP^C to PrP^Sc

limbs/digits/tail

short tibia ( J:333707 )

♀ • females show a significantly shorter tibia length (mm) than wild-type controls

growth/size/body

increased body fat mass ( J:333707 )

♂ • males show a significantly higher body fat mass (g) than wild-type controls

cardiovascular system

abnormal R wave ( J:333707 )

♂ • males exhibit a slight increase in mean R amplitude (mV), suggesting that the left ventricle is enlarged

adipose tissue

increased body fat mass ( J:333707 )

♂ • males show a significantly higher body fat mass (g) than wild-type controls

increased percent body fat/body weight ( J:333707 )

♂ • males show a significantly higher body fat percentage (%) than wild-type controls

hematopoietic system

increased Ly6C-positive immature NK cell number ( J:333707 )

♀ • females show a slight increase in CD11b- Ly6C+ NK cells

mortality/aging

increased susceptibility to infection induced morbidity/mortality ( J:333707 )

• after intracerebral inoculation with pathogenic PrP^Sc strains (Fukuoka-1 or Chandler), mice die significantly earlier than similarly inoculated wild-type controls, with an average survival of less than 150 days post inoculation (dpi)

nervous system

nervous system phenotype ( J:333707 )

N • brain histology showed no apparent abnormalities in the cortex, hippocampus, thalamus, cerebellum or medulla oblongata; no defects in prepulse inhibition or epileptic symptoms are observed