Mouse Genome Informatics
hm1
    Abcd1tm1Kds/Abcd1tm1Kds
either: (involves: 129S4/SvJae * C57BL/6) or (involves: 129/Sv * 129S4/SvJae * C57BL/6)
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• storage of very long-chain fatty acids in the adrenal gland, brain, kidney, heart and liver
• storage of very long-chain fatty acids in the adrenal gland, brain, kidney, heart and liver

Mouse Models of Human Disease
OMIM IDRef(s)
Adrenoleukodystrophy; ALD 300100 J:42479


Mouse Genome Informatics
hm2
    Abcd1tm1Kds/Abcd1tm1Kds
involves: 129/Sv * 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
behavior/neurological
• evident between 15 and 20 months of age
• on rotarod test, evident between 15 and 20 months of age
• reduced rearing, evident between 15 and 20 months of age

nervous system
• evident at 16 months of age, enlarged processes contained myelin-like figures
• evident at 16 months of age, in CNS
• evident at 16 months of age, in CNS, white matter had redundant sheaths that failed to contact axons and in PNS, focal hypermyelination of sciatic nerves
• evident at 15 months of age, increased latency of compound muscle action potential

Mouse Models of Human Disease
OMIM IDRef(s)
Adrenoleukodystrophy; ALD 300100 J:75388


Mouse Genome Informatics
cx3
    Abcd1tm1Kds/Y
Abcd2tm1Apuj/Abcd2tm1Apuj

involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• at 8 months of age, exhibit an even higher level of accumulation of very long chain fatty acids in the spinal cord (C24:0 and C26:0), sciatic nerve (C26:0), adrenal gland (C22:0, C24:0, and C26:0) and serum (C26:0) than seen in single homozygous Abcd1 or Abcd2 mutant mice (J:94583)
• accumulation of very long chain fatty acids (C26:0) in the dorsal root ganglia (J:104122)

nervous system
• marked increase in the number and size of microglia at 22 months of age
• marked increase in the number and size of astrocytes at 12 and 22 months of age
• spinal cord axon degeneration that is more severe than in single homozygous Abcd2 or hemizygous Abdc1 mutant mice
• at 12 months of age, exhibit a lower amplitude of the H-wave, indicating defective spinal somatosensory response/spinal reflex and functionally defective large proprioceptive sensory neurons at the dorsal root ganglia or their afferents
• the latency of motor waves and the sensitive nerve conduction velocities are slowed down at 12 months of age

behavior/neurological
• those mutants with more severe behavioral phenotypes, show exaggerated bilateral extension of fore and hind limbs when suspended by tails at 20 months of age
• 8 of 11 show slight whole body tremor around 20 months of age
• at 15 months of age, exhibit a significant increase in the time required to reach a platform along a balance bar
• at 20 months of age, 6 of 11 double mutants cannot perform the balance test because they freeze or fall repeatedly from the bar
• severe impairment on the rotarod at 15 months of age
• at 15 months of age display ventral recumbence, with the entire body flattened against the surface of the balance bar, and the hind and fore limbs wrapped laterally around the bar
• at 20 months of age, see postural hypotonia, characterized by lying flat on abdomen with fore and hind limbs splayed laterally, however muscle strength is no different from wild-type
• at 15 months of age, do not use the hind limbs when moving along a beam, instead use the fore limbs to drag themselves
• exhibit a decline in deambulation activity at 20 months of age
• at 15 months of age exhibit a marked tendency to slip off a balance bar, indicating ataxia
• in the open field, are less explorative than single hemizygous Abcd1 mutant mice and have a tendency to freezing
• significantly poorer rearing behaviors than wild-type at 20 months of age

endocrine/exocrine glands
• accumulation of lipid droplets across the adrenal cortex, encompassing glomerular, fascicular and reticular cell layers
• observe intralysosomal needle-like cholesterol inclusions spread all over the cytoplasm that occur about 10x more often than in hemizygous Abcd1 mutant males

immune system
• marked increase in the number and size of microglia at 22 months of age
• detect some inflammatory cell infiltrates of cervical and lumber spinal cord regions in small clusters adjacent to blood vessels and perimeningeal areas, composed mainly of T lymphocytes

hematopoietic system
• marked increase in the number and size of microglia at 22 months of age


Mouse Genome Informatics
cx4
    Abcd1tm1Kds/Abcd1tm1Kds
Slc27a2tm1Kds/Slc27a2tm1Kds

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• these mice were indistinguishable from wild-type


Mouse Genome Informatics
cx5
    Abcd1tm1Kds/Y
Slc27a2tm1Kds/Slc27a2tm1Kds

involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
normal phenotype
• these mice were indistinguishable from wild-type


Mouse Genome Informatics
ot6
    Abcd1tm1Kds/Y
either: (involves: 129S4/SvJae * C57BL/6) or (involves: 129/Sv * 129S4/SvJae * C57BL/6)
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype

Lipid clefts are seen in adrenocortical cells of Abcd1tm1Kds/Y mice

homeostasis/metabolism
• storage of very long-chain fatty acids in the adrenal gland, brain, kidney, heart and liver
• storage of very long-chain fatty acids in the adrenal gland, brain, kidney, heart and liver

Mouse Models of Human Disease
OMIM IDRef(s)
Adrenoleukodystrophy; ALD 300100 J:42479


Mouse Genome Informatics
ot7
    Abcd1tm1Kds/Y
involves: 129S4/SvJae * C57BL/6J
Key:
phenotype observed in females
phenotype observed in males
N normal phenotype
homeostasis/metabolism
• at 8 months of age, exhibit an accumulation of very long chain fatty acids in the spinal cord (C26:0), adrenal gland (C24:0 and C26:0), and sciatic nerve (C26:0)

behavior/neurological
• in rotarod test at 20 months of age
• impaired exploratory abilities in the open field test

endocrine/exocrine glands
• exhibit intralysosomal needle-like cholesterol inclusions in the fascicular cell layer of the cortex and cortico-medullary junction
• at 18 months of age, mice exhibit fibrosis of the fascicular cell layer
• mice exhibit intralysosomal needle-like cholesterol inclusions in the fascicular cell layer
• at 18 months of age, exhibit fibrosis of the reticular cell layer

nervous system
• slight increase in the number and size of microglia at 22 months of age
• slight increase in the number and size of astrocytes at 22 months of age
• axonal degeneration in the spinal cord and inflammatory infiltrates in cervical and lumbar spinal cord regions
• degeneration in the spinal cord, characterized by axonal swelling with accumulation of APP and synaptophysin and abnormal lipidic droplets resulting from myelin debris
• axonal degeneration precedes myelin disturbances
• spinal cord axons contain myelin debris
• exhibit slowing of motor and sensitive nerve conduction velocities at 20, but not 12, months of age

hematopoietic system
• slight increase in the number and size of microglia at 22 months of age

immune system
• slight increase in the number and size of microglia at 22 months of age

Mouse Models of Human Disease
OMIM IDRef(s)
Adrenoleukodystrophy; ALD 300100 J:94583