Phenotypes associated with this allele

• Allele Symbol: Stub1^tm1Cpat
• Allele Name: targeted mutation 1, Cam Patterson
• Allele ID: MGI:2680005
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Stub1^tm1Cpat/Stub1^tm1Cpat	involves: 129S/SvEv	MGI:5550148
hm2	Stub1^tm1Cpat/Stub1^tm1Cpat	involves: 129S/SvEv * C57BL/6	MGI:2680011

Genotype
MGI:5550148

hm1

• Allelic Composition: Stub1^tm1Cpat/Stub1^tm1Cpat
• Genetic Background: involves: 129S/SvEv

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

behavior/neurological

abnormal response to new environment ( J:206229 )

• mutants exhibit an aberrant pattern of exploration in a novel environment, showing increased time in the open arms of the elevated plus maze

impaired spatial learning ( J:206229 )

• mutants exhibit a higher error rate in the acquisition of a spatial learning task in the Barnes maze

decreased startle reflex ( J:206229 )

• magnitude of the acoustic startle response is reduced 86% in mutants compared to wild-type mice and the reaction time to the acoustic startle is delayed across all sound levels by an average of 40%

• however, prepulse inhibition levels are not affected, suggesting that sensory gating and auditory function are not impaired

ataxia ( J:206229 )

• cerebellar ataxia

impaired coordination ( J:206229 )

• mice show a severe motor impairment on the rotarod, with reduced latency to fall times and no improvement with retesting

short stride length ( J:206229 )

• mutants take smaller steps in gait testing, showing an 8-16% reduction in stride length, however show no differences in overlap, front paw stride length or front paw and hind paw base width

endocrine/exocrine glands

decreased testis weight ( J:206229 )

♂ • 38% decrease in testes weight

homeostasis/metabolism

decreased follicle stimulating hormone level ( J:206229 )

• follicle stimulating hormone levels are reduced more than 50% compared to wild-type mice, irrespective of gender

nervous system

abnormal cerebellum morphology ( J:206229 )

• cellular loss throughout the various lobes of the cerebellum, with especially noticeable degeneration in the Purkinje cell layer

• cerebellar regions that do contain intact Purkinje cells exhibit severe dendritic swelling

Purkinje cell degeneration ( J:206229 )

• 3-fold increase in the number of pyknotic nuclei in the Purkinje cell layer compared to wild-type

abnormal Purkinje cell dendrite morphology ( J:206229 )

• cerebellar regions that do contain intact Purkinje cells exhibit severe dendritic swelling

reproductive system

decreased testis weight ( J:206229 )

♂ • 38% decrease in testes weight

reduced fertility ( J:206229 )

• breeding pairs are unable to successfully mate

Genotype
MGI:2680011

hm2

• Allelic Composition: Stub1^tm1Cpat/Stub1^tm1Cpat
• Genetic Background: involves: 129S/SvEv * C57BL/6

mortality/aging

perinatal lethality, incomplete penetrance ( J:86213 )

• approximately 5% are cannibalized shortly after birth, putatively after perinatal death

postnatal lethality, incomplete penetrance ( J:86213 )

• incomplete penetrance

• 20% die within the first 10 days after birth

• lethality is not rescued by transfer to foster mothers

muscle

abnormal muscle fiber morphology ( J:245069 )

• quadriceps muscle show less subsarcolemmal mitochondria compared to controls

abnormal sarcoplasmic reticulum morphology ( J:245069 )

• 6 month old mice exhibit increased sarcoplasmic reticulum compartments in quadriceps muscle and gastrocnemius, with toxic oligomers and tubular aggregates, but not in soleus

abnormal skeletal muscle fiber type ratio ( J:245069 )

• muscle fiber composition in the gastrocnemius is affected, with most fibers having high levels of diffuse staining for ATPase and higher levels of COX content and strong NADH-TR staining

behavior/neurological

decreased fluid intake ( J:260672 )

• mice show a decrease in fluid intake, with cumulative fluid intake approximately 2.5-fold less than controls

renal/urinary system

increased urine creatinine level ( J:260672 )

increased urine chloride ion level ( J:260672 )

• increase in urine chloride level

• however, when urinary electrolyte concentrations are normalized to creatinine, no differences are seen

increased urine potassium level ( J:260672 )

• increase in urine potassium concentration

• however, when urinary electrolyte concentrations are normalized to creatinine, no differences are seen

increased urine sodium level ( J:260672 )

• increase in urine sodium level

• however, when urinary electrolyte concentrations are normalized to creatinine, no differences are seen

increased urine osmolality ( J:260672 )

• osmolality of spontaneous voided urine is higher, with average urine osmolality 1.5-fold greater than controls

• however, baseline serum electrolytes are normal

increased urine urea nitrogen level ( J:260672 )

• increase in urine baseline urea level

• however, when normalized to creatinine, no differences are seen

cellular

abnormal cell physiology ( J:86213 )

• fibroblasts show diminished responses to stress

• viability of fibroblasts after heat shock is reduced compared to wild-type and mutants only develop partial thermotolerance after preconditioning with a sublethal heat challenge

abnormal apoptosis ( J:86213 )

• apoptosis is observed in the thymii of deceased neonates

• increase in apoptosis of GI tract cells and splenocytes after thermal challenge

increased thymocyte apoptosis ( J:86213 )

• evidence of massive thymocyte apoptosis in deceased neonates

immune system

increased thymocyte apoptosis ( J:86213 )

• evidence of massive thymocyte apoptosis in deceased neonates

thymus atrophy ( J:86213 )

• atrophied in deceased neonates

thymus hypoplasia ( J:86213 )

• observe only in deceased neonates

hematopoietic system

increased thymocyte apoptosis ( J:86213 )

• evidence of massive thymocyte apoptosis in deceased neonates

thymus atrophy ( J:86213 )

• atrophied in deceased neonates

thymus hypoplasia ( J:86213 )

• observe only in deceased neonates

homeostasis/metabolism

increased urine creatinine level ( J:260672 )

increased urine chloride ion level ( J:260672 )

• increase in urine chloride level

• however, when urinary electrolyte concentrations are normalized to creatinine, no differences are seen

increased urine potassium level ( J:260672 )

• increase in urine potassium concentration

• however, when urinary electrolyte concentrations are normalized to creatinine, no differences are seen

increased urine sodium level ( J:260672 )

• increase in urine sodium level

• however, when urinary electrolyte concentrations are normalized to creatinine, no differences are seen

increased urine osmolality ( J:260672 )

• osmolality of spontaneous voided urine is higher, with average urine osmolality 1.5-fold greater than controls

• however, baseline serum electrolytes are normal

increased urine urea nitrogen level ( J:260672 )

• increase in urine baseline urea level

• however, when normalized to creatinine, no differences are seen

increased susceptibility to injury ( J:86213 )

• 100% of mutants die rapidly, either during or immediately after a thermal challenge of 42 degrees C for 15 minutes, putatively due to fluid shifts or endotoxemia resulting from compromised GI barrier

• mutants exhibit temperature sensitivity as indicated by impaired responses to thermal challenge resulting in stress-responsive lesions such as edema, hyperemia, increased apoptosis and small intestinal damage

endocrine/exocrine glands

increased thymocyte apoptosis ( J:86213 )

• evidence of massive thymocyte apoptosis in deceased neonates

thymus atrophy ( J:86213 )

• atrophied in deceased neonates

thymus hypoplasia ( J:86213 )

• observe only in deceased neonates

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
autosomal recessive spinocerebellar ataxia 16		DOID:0080029	OMIM:615768	J:245069