Phenotypes associated with this allele

• Allele Symbol: Pex5^tm1Pec
• Allele Name: targeted mutation 1, Peter Carmeliet
• Allele ID: MGI:2384516
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cn1	Pex5^tm1Pec/Pex5^tm1Pec Cnp^tm1(cre)Kan/Cnp^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3851811
cn2	Pex5^tm1Pec/Pex5^tm1Pec Plekha5^Tg(AMH-cre)1Flor/Plekha5^+	involves: 129S1/Sv * 129X1/SvJ	MGI:3851809
cn3	Pex5^tm1Pec/Pex5^tm1Pec Speer6-ps1^Tg(Alb-cre)21Mgn/Speer6-ps1^+	involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA	MGI:3851810

Genotype
MGI:3851811

cn1

• Allelic Composition: Pex5^tm1Pec/Pex5^tm1Pec; Cnp^tm1(cre)Kan/Cnp⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

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

mortality/aging

premature death ( J:123503 )

• 91% are dead by 12 months of age

• none survive past 13 months

behavior/neurological

tremors ( J:123503 )

• hind limb tremors develop after 12 months

ataxia ( J:123503 )

• hind limb ataxia in about 14% of mice by 3 months of age

• symptoms most obvious after 9 months

hindlimb paralysis ( J:123503 )

• hind limb paralysis develops eventually

hindlimb paresis ( J:123503 )

• hind limb paresis develops over 12 months

nervous system

abnormal glial cell morphology ( J:123503 )

abnormal oligodendrocyte morphology ( J:123503 )

• defective peroxisomes in oligodendrocytes

gliosis ( J:123503 )

• massive gliosis in areas of demyelination

microgliosis ( J:123503 )

• activated microglia and macrophage appear early

abnormal brain white matter morphology ( J:123503 )

• defects seen in rostral white matter by 4 months of age

• defects in the hippocampal commissure and cerebellar white matter less extensive

• defects become more extensive with time

• subcortical white matter degeneration increases as behavioral disorders progress

abnormal axon morphology ( J:123503 )

• axonal swelling appears early in the corpus callosum and spinal cord

• gradual loss of myelinated nerve fibers

abnormal myelination ( J:123503 )

• very long chain fatty acids become progressively increased in myelin

respiratory system

abnormal breathing pattern ( J:123503 )

• difficulty breathing develops after 12 months

skeleton

kyphosis ( J:123503 )

• becomes prevalent in mice over 12 months of age

immune system

microgliosis ( J:123503 )

• activated microglia and macrophage appear early

abnormal inflammatory response ( J:123503 )

• infiltration of T cells into demyelinated regions of the brain by 4 months

• B cell infiltration sometimes seen as well

• proinflammatory proteins become more abundant

hematopoietic system

microgliosis ( J:123503 )

• activated microglia and macrophage appear early

cellular

abnormal glial cell morphology ( J:123503 )

abnormal oligodendrocyte morphology ( J:123503 )

• defective peroxisomes in oligodendrocytes

gliosis ( J:123503 )

• massive gliosis in areas of demyelination

microgliosis ( J:123503 )

• activated microglia and macrophage appear early

Genotype
MGI:3851809

cn2

• Allelic Composition: Pex5^tm1Pec/Pex5^tm1Pec; Plekha5^{Tg(AMH-cre)1Flor}/Plekha5⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ

reproductive system

abnormal testis morphology ( J:108368 )

♂

abnormal seminiferous tubule morphology ( J:108368 )

♂ • large numbers of lipid drops present at 10 days and 7 weeks

seminiferous tubule degeneration ( J:108368 )

♂ • spermatozoa still present at 7 weeks

♂ • progressive degeneration of seminiferous tubules from 9-11 weeks

decreased testis weight ( J:108368 )

♂ • testicular weight 30-40% of normal controls at 14 weeks

male infertility ( J:108368 )

♂ • 6-13 week old males mate but fail to sire offspring

endocrine/exocrine glands

abnormal testis morphology ( J:108368 )

♂

abnormal seminiferous tubule morphology ( J:108368 )

♂ • large numbers of lipid drops present at 10 days and 7 weeks

seminiferous tubule degeneration ( J:108368 )

♂ • spermatozoa still present at 7 weeks

♂ • progressive degeneration of seminiferous tubules from 9-11 weeks

decreased testis weight ( J:108368 )

♂ • testicular weight 30-40% of normal controls at 14 weeks

Genotype
MGI:3851810

cn3

• Allelic Composition: Pex5^tm1Pec/Pex5^tm1Pec; Speer6-ps1^{Tg(Alb-cre)21Mgn}/Speer6-ps1⁺
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6 * DBA

growth/size/body

decreased body weight ( J:112503 )

• 30-40% lower than controls by 7 weeks of age

abnormal postnatal growth ( J:112503 )

• low body weight recovers to near normal between 7 weeks and 3 months

slow postnatal weight gain ( J:112503 )

• growth retardation starting about the third week after birth

enlarged liver ( J:112503 )

• hepatomegaly at 10 weeks

liver hyperplasia ( J:112503 )

• hypertrophic and hyperplastic hepatocytes particularly in pericentric region

liver/biliary system

liver/biliary system phenotype ( J:112503 )

N • mice appear healthy and fertile with normal liver function through 14 months of age

abnormal hepatocyte respiration ( J:121804 )

abnormal liver morphology ( J:112503 )

• possible compression of liver sinusoids

enlarged liver ( J:112503 )

• hepatomegaly at 10 weeks

liver hyperplasia ( J:112503 )

• hypertrophic and hyperplastic hepatocytes particularly in pericentric region

increased liver tumor incidence ( J:112503 )

• increased incidence after 12 months

cellular

abnormal cell morphology ( J:112503 )

• in the liver

abnormal endoplasmic reticulum morphology ( J:112503 )

• proliferation of smooth endoplasmic reticulum

abnormal mitochondrial inner membrane morphology ( J:112503 )

• tubulation of inner membrane

abnormal mitochondrial crista morphology ( J:112503 )

• reduced numbers of curled and stacked cristae

abnormal mitochondrial shape ( J:112503 )

• proliferation of pleomorphic mitochondria

• mitochondria are normal if catalase positive peroxisomes are present

abnormal lysosome morphology ( J:112503 )

• groups of lysoosomes as well as lipid drops observed

abnormal hepatocyte respiration ( J:121804 )

abnormal respiratory electron transport chain ( J:112503 )

• impaired respiratory chain

abnormal mitochondrial ATP synthesis coupled electron transport ( J:112503 )

• activity of mitchondrial complex II and IV are normal in the liver

• activity of mitochondrial complex I is less than 15% of normal in the liver at 20 weeks of age

• activity of mitochondria complex III and V about 40% normal

• reduced membrane potential of liver mitochondria

• reduced ATP production

abnormal fatty acid beta-oxidation ( J:121804 )

• beta oxidation in cultured hepatocytes is abnormal

homeostasis/metabolism

abnormal fatty acid beta-oxidation ( J:121804 )

• beta oxidation in cultured hepatocytes is abnormal

abnormal blood homeostasis ( J:112503 )

• whole blood pyruvate slightly decreased

increased circulating lactate level ( J:112503 )

• whole blood lactate is increased about 70%

abnormal glucose homeostasis ( J:112503 )

• increased activity of the glycolytic pathway

abnormal bile salt homeostasis ( J:121804 )

• bile acid metabolism is considerably reduced

neoplasm

increased liver tumor incidence ( J:112503 )

• increased incidence after 12 months