Phenotypes associated with this allele

• Allele Symbol: stu
• Allele Name: stumbler
• Allele ID: MGI:1857058
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	stu/stu	involves: C3H/HeJ	MGI:3805356
hm2	stu/stu	involves: C3H/HeJ * C57BL/6J	MGI:3835032

Genotype
MGI:3805356

hm1

• Allelic Composition: stu/stu
• Genetic Background: involves: C3H/HeJ

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

mortality/aging

postnatal lethality ( J:6464 , J:24754 )

• most homozygotes die before weaning (J:6464)

• Background Sensitivity: on the C3H/HeJ background homozygotes die by 21 days of age, but live slightly longer when crossed with C57BL/6J (J:24754)

behavior/neurological

abnormal righting response ( J:6464 )

• the righting response is delayed by a day or two so young homozygote have greater than normal difficulty in turning onto their feet

abnormal gait ( J:6464 )

• high stepping broad-based gait, stumbling locomotion found by 12 days of age

growth/size/body

decreased body weight ( J:6464 )

• homozygotes become less active, never gain as much weight as littermate controls, and this weight disparity is progressive

nervous system

abnormal Purkinje cell morphology ( J:24754 )

• Purkinje cells have reduced total volume, irregularly increased caliber, abnormal branching patterns of dendrites, high concentration of mitochondria in soma and dendrites, persistent somatic spines and filopodia at least to 21 days of age, and focal swellings on axons

abnormal Purkinje cell differentiation ( J:6464 )

• cerebeller Purkinje cells fail to mature and have swellings along the larger dendritic trunks, especially at the branch points, and short, spiny dendrites projecting from all parts of the soma

• an increase in the number of mitochondrial profiles in Purkinje cell soma even at 10 days of age

• Purkinje cell nuclei are often eccentrically positioned

abnormal Purkinje cell focal axonal swelling ( J:24754 )

abnormal Purkinje cell dendrite morphology ( J:24754 )

decreased Purkinje cell number ( J:24754 )

• total number of Purkinje cells is less than normal by 10 days of age

abnormal cerebellar granule cell morphology ( J:6464 , J:24754 )

• some granule cells appear to have longer than normal dendrites (J:6464)

• total number of granule cells is less than normal by 10 days of age (J:24754)

small cerebellum ( J:24754 )

• although smaller than normal, the cerebellum has a normal folial pattern

cellular

abnormal Purkinje cell differentiation ( J:6464 )

• cerebeller Purkinje cells fail to mature and have swellings along the larger dendritic trunks, especially at the branch points, and short, spiny dendrites projecting from all parts of the soma

• an increase in the number of mitochondrial profiles in Purkinje cell soma even at 10 days of age

• Purkinje cell nuclei are often eccentrically positioned

Genotype
MGI:3835032

hm2

• Allelic Composition: stu/stu
• Genetic Background: involves: C3H/HeJ * C57BL/6J

cellular

abnormal Purkinje cell mitochondrial morphology ( J:28094 )

nervous system

nervous system phenotype ( J:28094 )

N • the foliation of the cerebellar cortex is normal even though the size is small

thin external granule cell layer ( J:28094 )

• slightly thinner than normal at 10 to 13 days of age

abnormal cerebellar cortex morphology ( J:28094 )

• the length of all of the layers of the cerebellar cortex is shorter than normal

abnormal cerebellar Purkinje cell layer ( J:28094 )

abnormal Purkinje cell morphology ( J:28094 )

• Purkinje cells have disorganized endoplasmic reticulum and an increased number of mitochondria, although normal-looking synapses are found, and in homozygotes that live to 35 days of age near-normal looking Purkinje cells can be found

abnormal Purkinje cell mitochondrial morphology ( J:28094 )

Purkinje cell degeneration ( J:28094 )

• degenerating Purkinje cells are only seen after 19 days of age

abnormal Purkinje cell dendrite morphology ( J:28094 )

• at 9 days of age Purkinje cells have dendritic arborizations that appear immature, are much smaller than normal, and have somatic spines which can still be found at 23 days of age

decreased Purkinje cell number ( J:28094 )

• Purkinje cells never reach normal numbers

abnormal cerebellar granule layer morphology ( J:28094 )

thin cerebellar granule layer ( J:28094 )

• slightly thinner than normal from 10 to 23 days of age, and the volume of the granule layer is reduced in older homozygotes

abnormal cerebellar molecular layer ( J:28094 )

thin cerebellar molecular layer ( J:28094 )

• slightly thinner than normal at 10 to 23 days of age

small cerebellum ( J:28094 )

• after 10 days of age the cerebellum ceases to grow at the same rate as controls, which show rapid cerebellar growth overthe first 3 weeks of life, and thus the stumbler cerebellum is smaller than normal

• the smaller cerebellum is due primarily to a comparative reduction in number of Purkinje cells and granule cells

growth/size/body

decreased body weight ( J:28094 )

• as early as 9 days of age homozygotes are approximately 15% lighter than controls and by 23 days of age weigh only 40% that of controls