Mouse Genome Informatics
hm1
    Fig4plt1/Fig4plt1
B6.Cg-Fig4plt1
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype

Presence of vacuoles in the atria of E18.5 Fig4plt1/Fig4plt1 mutants

cardiovascular system
• significant degeneration of the atria with large, transparent vacuoles


Mouse Genome Informatics
hm2
    Fig4plt1/Fig4plt1
involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survive to 1 -2 months of age

nervous system
• extensive autophagic inclusion bodies
• thinning of the myelin sheath of the sciatic nerve
• thinning of the myelin sheath of the sciatic nerve
• severe spongiform degeneration in the brain and extensive loss of neurons from the peripheral ganglia
• extensive loss of neurons from peripheral ganglia
• neurons in layers 4 and 5 of the cortex, the deep cerebellar nuclei, and the dorsal root ganglia are severely affected with accumulation of vacuoles that fill the cytoplasm
• in the sciatic nerve

pigmentation

integument


Mouse Genome Informatics
hm3
    Fig4plt1/Fig4plt1
involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• all mice die by 6 weeks (J:122737)
• juvenile lethality at 6-8 weeks of age (J:185989)

behavior/neurological
• severe movement disorder by 30 days of age
• by 30 days of age (J:185989)
• progressive loss of mobility
• at week 3
• mice have a 'swimming' gait

nervous system
• at 6 weeks, spinal motor neurons accumulates vacuoles prior to cell loss
• visible at week 1, mice exhibit neonatal degeneration in sensory and autonomic ganglia with loss of neurons in from layers 4 and 5 of the cortex, deep cerebellar nuclei, thalamus, pons and medulla
• sciatic nerves have reduced amplitude of compound muscle action potential
• mice exhibit fewer large-diameter myelinated axons
• sciatic nerve conduction velocity is slowed
• in deep layers of cortex, cerebellar nuclei, hippocampus, brainstem, and dorsal root ganglia
• reduced sciatic nerve myelination
• low abundance of myelin basic protein
• sciatic nerves have reduced amplitude of compound muscle action potential
• sciatic nerve conduction velocity is slowed (J:122737)
• sciatic nerve conduction velocity reduced to 50% of velocity in control mice (J:185989)

muscle

growth/size/body

hematopoietic system
• severe tremors develop 2 weeks after birth

immune system
• severe tremors develop 2 weeks after birth

pigmentation
• at P3 (J:122737)
• clumps of melanosomes are visible in the few remaining pigmented hair follicles

integument
• at P3 (J:122737)
• clumps of melanosomes are visible in the few remaining pigmented hair follicles
• pigment containing hair follicles are decreased in number

Mouse Models of Human Disease
OMIM IDRef(s)
Charcot-Marie-Tooth Disease, Type 4j; CMT4J 611228 J:122737


Mouse Genome Informatics
hm4
    Fig4plt1/Fig4plt1
involves: 129P2/OlaHsd * C3H * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
growth/size/body
• relative overgrowth of incisors
• impaired growth; skeleton is normal at birth but is smaller at P21

craniofacial
• craniofacial morphology is altered
• relative overgrowth of incisors

hematopoietic system
• extensive vacuolization is seen in cultures of bone marrow mesenchymal stroma

skeleton
• skeleton is normal at birth but is smaller at P21
• clavicles are 20-25% smaller at P21 than in wild-type, however their shape is normal
• however, pelvic bone shape is normal in newborns and at P21
• long bones are 20-25% smaller at P21 than in wild-type
• bone volume fraction, bone surface, trabecular number and connectivity density are reduced to less than 50% of wild-type values
• lower cortical density of bones
• femoral cortical thickness is reduced to less than 50% of wild-type values
• extensive vacuolization is seen in cultures of isolated osteoblasts from calvarial tissue
• lower trabecular density of bones and reduction in size and density of trabeculae in vertebrae
• trabecular separation is increased more than 3-fold

limbs/digits/tail
N
• mice do not exhibit aplasia or hypoplasia of digits on the front or rear limb (J:203638)

Mouse Models of Human Disease
OMIM IDRef(s)
Yunis-Varon Syndrome; YVS 216340 J:203638


Mouse Genome Informatics
cx5
    Fig4plt1/Fig4plt1
Tg(ACTB-Fig4*I41T)705Mm/0

involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival is increased to 3?6 months compared to from 1?2 months in Fig4 null mice not carrying the transgene

nervous system
N
• unlike in null mice not carrying the transgene, myelin sheath thinning is not seen (J:173446)
• intermediate level of autophagic inclusion bodies
• high pressure hydrocephalus is indicated by the compression of the cerebellum and hippocampus
• intermediate level compared to null mice not carrying the transgene
• intermediate level of degeneration compared to null mice not carrying the transgene
• degeneration of the cerebellar nuclei
• reduced at 4 and 14 months of age in the sciatic nerve but not as much as in null mice not carrying the transgene

craniofacial

integument

pigmentation

skeleton

Mouse Models of Human Disease
OMIM IDRef(s)
Charcot-Marie-Tooth Disease, Type 4j; CMT4J 611228 J:173446


Mouse Genome Informatics
cx6
    Fig4plt1/Fig4plt1
Tg(ACTB-Fig4*I41T)721Mm/0

involves: 129 * C3H * C57BL/6J * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
N
• survival is completely corrected compared to Fig4 null mice not carrying the transgene (J:173446)

nervous system
N
• unlike in null mice not carrying the transgene, myelin sheath thinning is not seen (J:173446)
• a few autophagic inclusion bodies are present
• astrocytosis is almost completely corrected compared to null mice not carrying the transgene
• minimal spongiform degeneration unlike in null mice not carrying the transgene
• unlike in null mice not carrying the transgene, dorsal root ganglia are intact at P90
• degeneration of the cerebellar nuclei
• reduced at 4 and 14 months of age in the sciatic nerve but not as much as in null mice not carrying the transgene

pigmentation
• partial rescue of reduced pigmentation compared to null mice not carrying the transgene


Mouse Genome Informatics
cx7
    Fig4plt1/Fig4plt1
Tg(Eno2-Fig4)#Mm/?

involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• 65% of mice live 10 months or more

growth/size/body
• growth rate is improved during the first month relative to Fig4plt1 homozygotes

nervous system
N
• spongiform degeneration corrected at 3 weeks of age and in mice 9 and 12 months old (J:185989)
• dorsal root ganglion spongiform degeneration also improved (J:185989)
• sciatic nerve conduction velocity normal (J:185989)
• normal sciatic nerve myelination (J:185989)


Mouse Genome Informatics
cx8
    Fig4plt1/Fig4plt1
Tg(GFAP-Fig4)#Mm/?

involves: 129P2/OlaHsd * C3H * C57BL/6 * CAST/Ei * SJL
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• survival not corrected relative to Fig4plt1 homozygotes

growth/size/body
• growth not corrected relative to Fig4plt1 homozygotes

behavior/neurological
• severe movement disorder by 30 days of age
• by 30 days of age

nervous system
N
• astrogliosis mostly corrected (J:185989)
• reduced sciatic nerve myelination
• low abundance of myelin basic protein