Mouse Genome Informatics
hm1
    Slc19a2tm1Ejn/Slc19a2tm1Ejn
involves: 129S4/SvJae * 129S6/SvEvTac
Key:
phenotype observed in females WTSI Wellcome Trust Sanger Institute
phenotype observed in males EuPh Europhenome
N normal phenotype
mortality/aging
• on a diet containing 1.25 mg/kg or no thiamine homozygotes become extremely ill within 3-4 weeks or 17-18 days, respectively, with signs of illness appearing earlier than in wild-type mice

reproductive system
• on a normal diet testis size is about 65-75% smaller than wild-type (J:101675)
• reduced testis size is more severe on a thiamine deficient diet (J:101675)
• on either a thiamine replete or deficient diet no mature spermatocytes are found and degenerating germ cell are seen (J:101675)
• on a thiamine deficient diet many seminiferous tubules contain only Sertoli cells (J:101675)
• germ cells progress to the pachytene stage but no haploid spermatids are found (J:101675)
• males, but not females, are infertile (J:101675)

hematopoietic system
• after 2 weeks on a thiamine deficient diet, the number of pronormoblasts in homozygotes is decreased >10-fold and the number of basophilic normoblasts is decreased from 8.9% to 1.1% relative to wild-type mice
• however, no ringed sideroblasts are seen with Perl's Prussian blue staining nor iron granules are seen in circulating red blood cells
• after 2 weeks on a thiamine deficient diet, homozygotes develop decreased red cell counts
• however, on a thiamine replete diet hematological parameters and blood glucose are normal
• after 2 weeks on a thiamine deficient diet homozygotes develop a slight but significant increase in platelet numbers

endocrine/exocrine glands
• on a normal diet testis size is about 65-75% smaller than wild-type (J:101675)
• reduced testis size is more severe on a thiamine deficient diet (J:101675)

hearing/vestibular/ear
• by 19 days on a low thiamine diet, homozygotes exhibit progressive IHC loss in the apical half of the cochlea
• by 26 days on a low thiamine diet, IHC loss is nearly complete throughout most of the mid-cochlear region, while the basal 1/3 of the cochlea remains intact
• by 36 days, slight extension of IHC loss is noted in the basal cochlear extreme
• by 36 days on a low thiamine diet, homozygotes exhibit extensive OHC loss
• OHC loss progresses at a significantly slower rate than IHC loss which rises between 19 and 26 days after the onset of a low thiamine diet
• after 11 days on a low-thiamine diet (2 vs. 22 mg/kg in normal chow), homozygotes show elevated ABR thresholds by ~40 dB esp. for frequencies <22 kHz, whereas wild-type mice display no threshold elevations, even after 26 days
• after 26 days on a low-thiamine diet, homozygotes exhibit ABR threshold shifts of ~50 dB at 11.3 and 16 kHz
• on a low-thiamine diet, mutant ABR wave 1 latencies remain normal even when thresholds are elevated by 30-40 dB
• only partial recovery of ABR thresholds is observed after reintroduction of thiamin to a low-thiamine diet for 19 days
• on a normal thiamine diet or a thiamine-enriched diet (3 mg/kg), homozygotes show no significant ABR threshold differences relative to wild-type, even at >70 days on the diet
• after 26 days on a low-thiamine diet, homozygotes exhibit DPOAE shifts of 10-20 dB relative to wild-type mice
• DPOAE shifts are smaller than the shifts observed in ABR thresholds
• however, on a normal thiamine diet or a thiamine-enriched diet (3 mg/kg), homozygotes show no significant DPOAE threshold differences relative to wild-type, even at >70 days on the diet
• homozygotes display a rare form of sensorineural hearing loss, with selective IHC loss after 1-2 weeks on a low thiamine diet, and significantly greater IHC than OHC loss after prolonged thiamine deprivation

nervous system
• by 19 days on a low thiamine diet, homozygotes exhibit progressive IHC loss in the apical half of the cochlea
• by 26 days on a low thiamine diet, IHC loss is nearly complete throughout most of the mid-cochlear region, while the basal 1/3 of the cochlea remains intact
• by 36 days, slight extension of IHC loss is noted in the basal cochlear extreme
• by 36 days on a low thiamine diet, homozygotes exhibit extensive OHC loss
• OHC loss progresses at a significantly slower rate than IHC loss which rises between 19 and 26 days after the onset of a low thiamine diet

Mouse Models of Human Disease
OMIM IDRef(s)
NOT Thiamine-Responsive Megaloblastic Anemia Syndrome; TRMA 249270 J:101675