Phenotypes associated with this allele

• Allele Symbol: Abcd1^tm1Kds
• Allele Name: targeted mutation 1, Kirby D Smith
• Allele ID: MGI:2155926
• Summary: 7 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Abcd1^tm1Kds/Abcd1^tm1Kds	either: (involves: 129S4/SvJae * C57BL/6) or (involves: 129/Sv * 129S4/SvJae * C57BL/6)	MGI:2446588
hm2	Abcd1^tm1Kds/Abcd1^tm1Kds	involves: 129/Sv * 129S4/SvJae * C57BL/6J	MGI:2680904
cx3	Abcd1^tm1Kds/Y Abcd2^tm1Apuj/Abcd2^tm1Apuj	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J	MGI:3617309
cx4	Abcd1^tm1Kds/Abcd1^tm1Kds Slc27a2^tm1Kds/Slc27a2^tm1Kds	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J	MGI:3029427
cx5	Abcd1^tm1Kds/Y Slc27a2^tm1Kds/Slc27a2^tm1Kds	involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J	MGI:3029429
ot6	Abcd1^tm1Kds/Y	either: (involves: 129S4/SvJae * C57BL/6) or (involves: 129/Sv * 129S4/SvJae * C57BL/6)	MGI:2446589
ot7	Abcd1^tm1Kds/Y	involves: 129S4/SvJae * C57BL/6J	MGI:3617307

Genotype
MGI:2446588

hm1

• Allelic Composition: Abcd1^tm1Kds/Abcd1^tm1Kds
• Genetic Background: either: (involves: 129S4/SvJae * C57BL/6) or (involves: 129/Sv * 129S4/SvJae * C57BL/6)

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

homeostasis/metabolism

abnormal lipid homeostasis ( J:42479 )

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

increased saturated fatty acids level ( J:42479 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adrenoleukodystrophy		DOID:10588	OMIM:300100	J:42479

Genotype
MGI:2680904

hm2

• Allelic Composition: Abcd1^tm1Kds/Abcd1^tm1Kds
• Genetic Background: involves: 129/Sv * 129S4/SvJae * C57BL/6J

behavior/neurological

abnormal motor coordination/balance ( J:75388 )

♀ • evident between 15 and 20 months of age

impaired coordination ( J:75388 )

♀ • on rotarod test, evident between 15 and 20 months of age

decreased vertical activity ( J:75388 )

♀ • reduced rearing, evident between 15 and 20 months of age

nervous system

abnormal Schwann cell morphology ( J:75388 )

♀ • evident at 16 months of age, enlarged processes contained myelin-like figures

axon degeneration ( J:75388 )

♀ • evident at 16 months of age, in CNS

abnormal myelination ( J:75388 )

♀ • 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

abnormal nerve conduction ( J:75388 )

♀ • evident at 15 months of age, increased latency of compound muscle action potential

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adrenoleukodystrophy		DOID:10588	OMIM:300100	J:75388

Genotype
MGI:3617309

cx3

• Allelic Composition: Abcd1^tm1Kds/Y; Abcd2^tm1Apuj/Abcd2^tm1Apuj
• Genetic Background: involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J

homeostasis/metabolism

increased fatty acids level ( J:94583 , J:104122 )

♂ • 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

abnormal CNS glial cell morphology ( J:104122 )

♂

abnormal microglial cell morphology ( J:94583 )

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

abnormal astrocyte morphology ( J:94583 )

♂ • marked increase in the number and size of astrocytes at 12 and 22 months of age

astrocytosis ( J:94583 )

♂

axon degeneration ( J:94583 )

♂ • spinal cord axon degeneration that is more severe than in single homozygous Abcd2 or hemizygous Abdc1 mutant mice

abnormal nervous system physiology ( J:94583 )

♂

abnormal nervous system electrophysiology ( J:104122 )

♂ • 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

abnormal nerve conduction ( J:94583 )

♂ • the latency of motor waves and the sensitive nerve conduction velocities are slowed down at 12 months of age

behavior/neurological

abnormal involuntary movement ( J:104122 )

♂ • 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

tremors ( J:104122 )

♂ • 8 of 11 show slight whole body tremor around 20 months of age

impaired balance ( J:104122 )

♂ • 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

impaired coordination ( J:94583 )

♂ • severe impairment on the rotarod at 15 months of age

abnormal posture ( J:104122 )

♂ • 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

abnormal locomotor behavior ( J:104122 )

♂ • 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

ataxia ( J:104122 )

♂ • at 15 months of age exhibit a marked tendency to slip off a balance bar, indicating ataxia

abnormal locomotor activation ( J:94583 )

♂ • in the open field, are less explorative than single hemizygous Abcd1 mutant mice and have a tendency to freezing

decreased vertical activity ( J:104122 )

♂ • significantly poorer rearing behaviors than wild-type at 20 months of age

endocrine/exocrine glands

abnormal adrenal cortex morphology ( J:94583 )

♂ • 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

abnormal microglial cell morphology ( J:94583 )

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

increased inflammatory response ( J:94583 )

♂ • 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

abnormal microglial cell morphology ( J:94583 )

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

Genotype
MGI:3029427

cx4

• Allelic Composition: Abcd1^tm1Kds/Abcd1^tm1Kds; Slc27a2^tm1Kds/Slc27a2^tm1Kds
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:83438 )

♀ • these mice were indistinguishable from wild-type

Genotype
MGI:3029429

cx5

• Allelic Composition: Abcd1^tm1Kds/Y; Slc27a2^tm1Kds/Slc27a2^tm1Kds
• Genetic Background: involves: 129S4/SvJae * 129S6/SvEvTac * C57BL/6J

normal phenotype

no abnormal phenotype detected ( J:83438 )

♂ • these mice were indistinguishable from wild-type

Genotype
MGI:2446589

ot6

• Allelic Composition: Abcd1^tm1Kds/Y
• Genetic Background: either: (involves: 129S4/SvJae * C57BL/6) or (involves: 129/Sv * 129S4/SvJae * C57BL/6)

Lipid clefts are seen in adrenocortical cells of Abcd1^tm1Kds/Y mice

homeostasis/metabolism

abnormal lipid homeostasis ( J:42479 )

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

increased saturated fatty acids level ( J:42479 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adrenoleukodystrophy		DOID:10588	OMIM:300100	J:42479

Genotype
MGI:3617307

ot7

• Allelic Composition: Abcd1^tm1Kds/Y
• Genetic Background: involves: 129S4/SvJae * C57BL/6J

homeostasis/metabolism

increased fatty acids level ( J:94583 )

♂ • 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

impaired coordination ( J:94583 )

♂ • in rotarod test at 20 months of age

abnormal locomotor activation ( J:94583 )

♂ • impaired exploratory abilities in the open field test

endocrine/exocrine glands

abnormal adrenal cortex morphology ( J:94583 )

♂ • exhibit intralysosomal needle-like cholesterol inclusions in the fascicular cell layer of the cortex and cortico-medullary junction

abnormal adrenal gland zona fasciculata morphology ( J:94583 )

♂ • 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

abnormal adrenal gland zona reticularis morphology ( J:94583 )

♂ • at 18 months of age, exhibit fibrosis of the reticular cell layer

nervous system

abnormal microglial cell morphology ( J:94583 )

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

abnormal astrocyte morphology ( J:94583 )

♂ • slight increase in the number and size of astrocytes at 22 months of age

astrocytosis ( J:94583 )

♂

abnormal spinal cord morphology ( J:94583 )

♂ • axonal degeneration in the spinal cord and inflammatory infiltrates in cervical and lumbar spinal cord regions

axon degeneration ( J:94583 )

♂ • 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

abnormal nervous system physiology ( J:94583 )

♂

abnormal myelination ( J:94583 )

♂ • spinal cord axons contain myelin debris

abnormal nerve conduction ( J:94583 )

♂ • exhibit slowing of motor and sensitive nerve conduction velocities at 20, but not 12, months of age

hematopoietic system

abnormal microglial cell morphology ( J:94583 )

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

immune system

abnormal microglial cell morphology ( J:94583 )

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

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
adrenoleukodystrophy		DOID:10588	OMIM:300100	J:94583