Phenotypes associated with this allele

• Allele Symbol: Atl1^tm1.1Cbla
• Allele Name: targeted mutation 1.1, Craig Blackstone
• Allele ID: MGI:7463984
• Summary: 3 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Atl1^tm1.1Cbla/Atl1^tm1.1Cbla	C57BL/6-Atl1^tm1.1Cbla	MGI:7464769
cx2	Atl1^tm1.1Cbla/Atl1^tm1.1Cbla Reep1^Gt(OST398247)Tigm/Reep1^Gt(OST398247)Tigm	B6.Cg-Reep1^Gt(OST398247)Tigm Atl1^tm1.1Cbla	MGI:7464784
cx3	Atl1^tm1.1Cbla/Atl1^+ Reep1^Gt(OST398247)Tigm/Reep1^Gt(OST398247)Tigm	B6.Cg-Reep1^Gt(OST398247)Tigm Atl1^tm1.1Cbla	MGI:7464788

Genotype
MGI:7464769

hm1

• Allelic Composition: Atl1^tm1.1Cbla/Atl1^tm1.1Cbla
• Genetic Background: C57BL/6-Atl1^tm1.1Cbla

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

nervous system

abnormal corticospinal tract morphology ( J:334532 )

• mice show rare transverse endoplasmic reticulum (ER) structures in corticospinal axons

cellular

abnormal endoplasmic reticulum morphology ( J:334532 )

• mice show rare transverse ER structures in corticospinal axons

behavior/neurological

behavior/neurological phenotype ( J:334532 )

N • mice show no significant behavioral changes

Genotype
MGI:7464784

cx2

• Allelic Composition: Atl1^tm1.1Cbla/Atl1^tm1.1Cbla; Reep1^{Gt(OST398247)Tigm}/Reep1^{Gt(OST398247)Tigm}
• Genetic Background: B6.Cg-Reep1^{Gt(OST398247)Tigm} Atl1^tm1.1Cbla

adipose tissue

decreased white adipose tissue amount ( J:334532 )

• decrease in abdominal white fat deposits

behavior/neurological

limb grasping ( J:334532 )

• mice show prominent and progressive hindlimb clasping from 8 weeks of age

impaired coordination ( J:334532 )

• mice show impairments in rotarod performance as early as 4 weeks of age, falling from the rotarod much earlier than wild-type mice

• mice show compromised ability to walk on a cage ledge starting from 4 weeks and worsening over time

abnormal locomotor behavior ( J:334532 )

• 7 of 8 males and all females are unable to run at the lowest treadmill speed at 24 weeks of age

hindlimb paresis ( J:334532 )

spasticity ( J:334532 )

• mice exhibit difficulty with ambulation, exhibiting hindlimb weakness and stiff, slow movements characteristic of spasticity

cardiovascular system

abnormal pulmonary artery morphology ( J:334532 )

♀ • female mice exhibit lung arterial hyperplasia and hypertrophy

cellular

abnormal endoplasmic reticulum morphology ( J:334532 )

• mice show transverse endoplasmic reticulum (ER) expansion in myelinated corticospinal axons; transverse ER manifests as a pattern repeating about every 0.3-1 um across nearly the full diameter of the axon, resembling the rungs of a ladder in longitudinal sections

• ER in axons shows prominent transverse, sheet-like structures and these periodic structures are connected to one another via a few longitudinal ER tubules and have apertures that allow mitochondria, microtubules and neurofilaments to pass through

• the vast majority of corticospinal axons and only a few ventral root axons have expanded transverse ER

• transverse ER expansions are present in lumbar (L5) and cervical (C4) spinal cord at 1 month of age but are larger and more numerous at 6 months and transverse ER is more prominent in lumbar regions

• transverse ER is also present in spinothalamic axons in spinal cord as well as peripherally in sciatic nerve

• transverse axonal ER expansions sometimes are associated with, or give rise to, less-organized ER tubule aggregations at 6 months of age

increased endoplasmic reticulum stress ( J:334532 )

• levels of ER stress protein GRP78/immunoglobulin-binding protein (BiP) are increased, indicating ER stress in the spinal cord, however at P180, levels are dramatically decreased in the spinal cord

growth/size/body

decreased body weight ( J:334532 )

• mice show lower body weights starting at 8 weeks in males and 16 weeks in females

muscle

abnormal muscle morphology ( J:334532 )

• muscle wasting

skeletal muscle atrophy ( J:334532 )

• skeletal muscle atrophy of the front and hind limbs

nervous system

abnormal corticospinal tract morphology ( J:334532 )

• corticospinal tracts exhibit prominent changes in shape and size of axons and degeneration by 6 months of age

• transverse endoplasmic reticulum (ER) expansion is seen in myelinated corticospinal axons

• mitochondria appear more fragmented in corticospinal axons and mitochondrial volume is slightly increased in corticospinal axons, with more dramatic decreases in mitochondrial length

• however, ER-mitochondrial contact surfaces areas are similar to wild-type

abnormal myelin sheath morphology ( J:334532 )

• mice have multiple swollen myelin sheaths and digestion chambers in the peripheral nervous system

axonal spheroids ( J:334532 )

• 4.5-month-old mice have rare to occasional spheroids in the brainstem as well as in the spinal cord

reproductive system

reduced fertility ( J:334532 )

• about 30-50% of breeding pairs are poor breeders

• mice have short breeding periods (from ages 2-5 months)

respiratory system

hyperpnea ( J:334532 )

• mice exhibit rapid breathing while on a treadmill

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
hereditary spastic paraplegia		DOID:2476	OMIM:PS303350	J:334532

Genotype
MGI:7464788

cx3

• Allelic Composition: Atl1^tm1.1Cbla/Atl1⁺; Reep1^{Gt(OST398247)Tigm}/Reep1^{Gt(OST398247)Tigm}
• Genetic Background: B6.Cg-Reep1^{Gt(OST398247)Tigm} Atl1^tm1.1Cbla

behavior/neurological

abnormal motor capabilities/coordination/movement ( J:334532 )

• mice show progressive defects in motor function, but less severely than in double homozygotes

impaired coordination ( J:334532 )

• mice exhibit compromised ability to walk on the cage ledge beginning at 8 weeks for males and 16 weeks for females

• mice show impairments in rotarod performance, falling from the rotarod earlier than wild-type mice