Mouse Genome Informatics
hm1
    Cln3tm1Blda/Cln3tm1Blda
B6.129-Cln3tm1Blda
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
behavior/neurological
• at 30 mg/kg pentatilentetrazole all mice exhibit grade two seizures compared to only 50% of wild-type mice, mice develop seizures more quickly (93.8+/-6.5 s compared to 196.2+/-19.7 s in wild-type mice) and seizures last longer (425+/-70.3 s compared to 202.5+/-40.9 s in wild-type mice)
• when given free access to water, mice consume significantly more water over a 24 hr period than wild-type controls
• 40% of mice clasp at 4 months of age and 80% by 8 months whereas no heterozygotes clasp at 4 months and only one showed clasping behavior at 8 months
• mice exhibit higher tremor amplitudes than heterozygous mice at 5, 10 and 12 months with effects more pronounced with age
• while mice have no motor deficit when tested on a rotarod at 1 month, by 2 months mice are significantly impaired and by 10 months mice are impaired to levels 50% of heterozygotes
• at 10 months of age nocturnal activity is decreased by 50% compared to in heterozygotes
• however, daytime activity is normal

nervous system
• at 30 mg/kg pentatilentetrazole all mice exhibit grade two seizures compared to only 50% of wild-type mice, mice develop seizures more quickly (93.8+/-6.5 s compared to 196.2+/-19.7 s in wild-type mice) and seizures last longer (425+/-70.3 s compared to 202.5+/-40.9 s in wild-type mice)
• autofluorescent storage material accumulates within cells in the brain appearing earliest and most prominently in the CA3 region of the hippocampus as well as in the thalamus, raphe nucleus, parasubiculum, presubiculum, red nucleus, and regions of the cerebral cortex

cellular
• TPP1 levels the cerebral lysates increase more dramatically over time (6.8-fold compared to 2.9-fold in wild-type mice)

renal/urinary system
N
• under hypertonic conditions, primary cultures of epithelial cells of the kidney inner medulla exhibit no defects in osmolyte accumulation relative to wild-type type cells (J:160849)
• no difference in taurine uptake or efflux is detected between primary renal inner medullary cells from wild-type and mutant mice (J:160849)
• when given free access to water, mice exhibit a significantly lower fractional excretion of K+ than wild-type controls
• when given free access to water, mice exhibit lower urine osmolality than wild-type controls
• however, after 24 hrs of water deprivation urine osmolality increases to levels similar to those in wild-type controls
• at ~8 weeks of age, mice exhibit intracellular autofluorescent deposits in all kidney regions (including the renal cortex, outer and inner medulla, and renal papilla), unlike wild-type controls
• by 6 months of age, accumulation of autofluorescent inclusions is more extensive in all kidney regions
• when given free access to water, mice produce more urine over a 24 hr period than wild-type controls
• however, after 24 hrs of water deprivation urine volume is similar to that in wild-type controls

homeostasis/metabolism
• after 24 hrs of water deprivation, mice show significantly increased serum osmolarity relative to wild-type controls
• after 24 hrs of water deprivation, mice show significantly increased serum K+ relative to wild-type controls
• when given free access to water, mice exhibit a significantly lower fractional excretion of K+ than wild-type controls
• when given free access to water, mice exhibit lower urine osmolality than wild-type controls
• however, after 24 hrs of water deprivation urine osmolality increases to levels similar to those in wild-type controls

Mouse Models of Human Disease
OMIM IDRef(s)
Ceroid Lipofuscinosis, Neuronal, 3; CLN3 204200 J:125194