Phenotypes associated with this allele

• Allele Symbol: Abcd2^tm1Apuj
• Allele Name: targeted mutation 1, Aurora Pujol
• Allele ID: MGI:3612442
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Abcd2^tm1Apuj/Abcd2^tm1Apuj	involves: 129S1/Sv * 129X1/SvJ * C57BL/6J	MGI:3617308
cx2	Abcd1^tm1Kds/Y Abcd2^tm1Apuj/Abcd2^tm1Apuj	involves: 129S1/Sv * 129S4/SvJae * 129X1/SvJ * C57BL/6J	MGI:3617309

Genotype
MGI:3617308

hm1

• Allelic Composition: Abcd2^tm1Apuj/Abcd2^tm1Apuj
• Genetic Background: involves: 129S1/Sv * 129X1/SvJ * C57BL/6J

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

homeostasis/metabolism

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

• at 8 months of age, exhibit an accumulation of very long chain fatty acids (C22:0 and C24:0) in the adrenal gland, however no differences in spinal cord, sciatic nerve or serum levels (J:94583)

• accumulation of very long chain fatty acids (C26:0) in the dorsal root ganglia (J:104122)

nervous system

abnormal cerebellar Purkinje cell layer ( J:104122 )

• at 20 months of age, but not at 12 months of age, observe gaps in the Purkinje cell layer

abnormal Purkinje cell morphology ( J:104122 )

• reduction of non-phosphorylated neurofilaments in Purkinje cells, indicationg reduced dendrititc arborization

Purkinje cell degeneration ( J:104122 )

• local degeneration of Purkinje cells

abnormal CNS glial cell morphology ( J:104122 )

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:104122 )

• see reactive astrogliosis at 20 months of age in the spinal cord dorsal and ventral columns and the cerebellum

gliosis ( J:104122 )

• local reactive gliosis in the cerebellum

abnormal axon morphology ( J:104122 )

• accumulation of APP and synaptophysin, neurofilaments and organells in axonal swellings

neuron degeneration ( J:104122 )

• late-onset, slowly progressive neuronal degeneration

• degeneration of dorsal root ganglia neurons is evident at 20 months of age, characterized by an accumulation of residual and zebra-like bodies in both satellite cells and ganglia neurons, degenerative mitochondria that contain lipidic inclusions, disturbed endoplasmic reticulum and Golgi apparatus, and an increase in lysosomes

abnormal dorsal root ganglion morphology ( J:104122 )

• accumulation of very long chain fatty acids (C26:0) and degeneration of the dorsal root ganglia

axon degeneration ( J:94583 , J:104122 )

• spinal cord axon degeneration with a similar type of pathology found in hemizygous Abcd1 mutant males (J:94583)

• evident at 20 months of age in the dorsal root ganglia, characterized by axolemma decompaction, and in the spinal cord dorsal and ventral columns, as evidenced by axonal swellings (J:104122)

abnormal nervous system physiology ( J:104122 )

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

• latency of the H-wave is normal at 12 months of age but diminishes with age

behavior/neurological

tremors ( J:104122 )

• 3 of 14 show slight whole body tremor around 20 months of age

abnormal motor coordination/balance ( J:104122 )

impaired balance ( J:104122 )

• at 15 months of age, often fail to maintain balance and fall off a balance bar

impaired coordination ( J:104122 )

• at 12 months of age, display impaired performance during a 4 day trial on a rotating rod set at an accelerating speed

abnormal posture ( J:104122 )

• 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

abnormal locomotor behavior ( J:104122 )

• do not use the hind limbs when moving along a beam, instead use the fore limbs to drag themselves

ataxia ( J:104122 )

• late-onset (15 months) cerebellar and sensory ataxia

hyperactivity ( J:104122 )

• at 12 months of age, are significantly more active, especially after the first 5-min period, indicating lack of habituation capacity to a new environment

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

Genotype
MGI:3617309

cx2

• 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