Phenotypes associated with this allele

• Allele Symbol: Tg(tetO-FMR1*,-EGFP)#Rkhu
• Allele Name: transgene insertion, Renate K Hukema
• Allele ID: MGI:5751860
• Summary: 2 genotypes

Jump to	Allelic Composition	Genetic Background	Genotype ID
cx1	Tg(Prnp-rtTA2S*M2)#Rkhu/0 Tg(tetO-FMR1*,-EGFP)#Rkhu/0	involves: C57BL/6JRj	MGI:5752054
cx2	Tg(Hnrnpa2b1-rtTA2S*M2)9Jstr/0 Tg(tetO-FMR1*,-EGFP)#Rkhu/0	involves: C57BL/6JRj * FVB/N	MGI:5751863

Genotype
MGI:5752054

cx1

• Allelic Composition: Tg(Prnp-rtTA2S*M2)#Rkhu/0; Tg(tetO-FMR1*,-EGFP)#Rkhu/0
• Genetic Background: involves: C57BL/6JRj

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

behavior/neurological

abnormal optokinetic reflex ( J:224760 )

• 20 weeks of dox treatment results in a lower gain of optokinetic reflex, indicating deficits in compensatory eye movements

• discontinuing dox induction after 8 weeks of exposure results in better optokinetic reflex performance at 20 weeks

abnormal vestibuloocular reflex ( J:224760 )

• mice exhibit a lower gain in visually enhanced vestibulo-ocular reflex (VVOR) after 20 weeks of dox treatment

• discontinuing dox induction after 8 weeks of exposure prevents further deterioration of VVOR

hearing/vestibular/ear

abnormal vestibuloocular reflex ( J:224760 )

• mice exhibit a lower gain in visually enhanced vestibulo-ocular reflex (VVOR) after 20 weeks of dox treatment

• discontinuing dox induction after 8 weeks of exposure prevents further deterioration of VVOR

nervous system

neuronal intranuclear inclusions ( J:224760 )

• mice exhibit ubiquitin-positive intranuclear inclusions in the brain (lobule X of the cerebellum, hippocampus and striatum) after 8 weeks of doxycycline (dox) treatment

• intranuclear inclusions are round/spherical in shape in the hippocampus and cat-eye shaped in the granular layer of lobule X of the cerebellum

• the number of inclusions and size of inclusions increase with longer dox treatment times

• ubiquitin-positive intranuclear inclusions contain polyglycine peptides, the 20S core complex of the proteasome, Hsp40, and Rad23B

• 12 weeks of dox washout after both 12 and 16 weeks of dox treatment does not reduce the number or size of ubiquitin-positive inclusions in cerebellar lobule X, however further increase in number and size is not seen, indicating prevention of further progression

• 12 weeks of dox washout after 8 weeks of dox treatment results in a reduction in the number and size of ubiquitin-positive inclusions

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fragile X-associated tremor/ataxia syndrome		DOID:0050879	OMIM:300623	J:224760

Genotype
MGI:5751863

cx2

• Allelic Composition: Tg(Hnrnpa2b1-rtTA2S*M2)9Jstr/0; Tg(tetO-FMR1*,-EGFP)#Rkhu/0
• Genetic Background: involves: C57BL/6JRj * FVB/N

growth/size/body

weight loss ( J:229379 )

• mice treated with doxycycline (dox) starting at 3 weeks of age begin to lose weight after 2 days of dox treatment

liver/biliary system

abnormal liver morphology ( J:229379 )

• marker analysis indicates mitochondrial dysfunction in the liver of dox treated mice

hepatic steatosis ( J:229379 )

• mice treated with dox exhibit mild liver steatosis

pale liver ( J:229379 )

• livers are pale and pink in mice treated with dox

mortality/aging

premature death ( J:229379 )

• mice treated with dox starting at 3 weeks of age die after 5 days of dox treatment

nervous system

nervous system phenotype ( J:229379 )

N • ubiquitin positive inclusions are not seen in mice treated with dox for 4 days

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
fragile X-associated tremor/ataxia syndrome		DOID:0050879	OMIM:300623	J:229379