Phenotypes Associated with This Genotype

Genotype
MGI:3033364

• Allelic Composition: Slc19a2^tm1Gelb/Slc19a2^tm1Gelb
• Genetic Background: involves: 129X1/SvJ

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

mortality/aging

premature death ( J:79974 )

• life span is normal on a normal diet

• death occurs after 3-4 weeks on a thiamin deficient diet

cellular

azoospermia ( J:87410 )

♂ • no sperm in the epididymis at 12 weeks of age

abnormal spermatid morphology ( J:87410 )

♂ • absent

arrest of male meiosis ( J:87410 )

♂ • no metaphase I or metaphase II germ cells seen

♂ • severely reduced number of mid pachytene spermatocytes

♂ • on a thiamin deficient diet, spermatocyte loss occurred at an even earlier stage

behavior/neurological

ataxia ( J:79974 )

• after 4-5 weeks on a normal diet

• after about 17 days on a thiamin deficient diet

reproductive system

abnormal reproductive system morphology ( J:87410 )

decreased testis weight ( J:87410 )

♂ • half normal weight

♂ • many apoptotic cells in the tubules

abnormal spermatogenesis ( J:87410 )

♂ • completely disrupted

azoospermia ( J:87410 )

♂ • no sperm in the epididymis at 12 weeks of age

abnormal spermatid morphology ( J:87410 )

♂ • absent

arrest of male meiosis ( J:87410 )

♂ • no metaphase I or metaphase II germ cells seen

♂ • severely reduced number of mid pachytene spermatocytes

♂ • on a thiamin deficient diet, spermatocyte loss occurred at an even earlier stage

male infertility ( J:87410 )

♂ • on any diet

♂ • male fertility was totally restored by a minimum of 20 days on a high thiamin diet

hearing/vestibular/ear

impaired hearing ( J:79974 )

• normal auditory-evoked brainstem response on a normal diet

• hearing loss on a thiamin deficient diet

• recovery from hearing loss after restoration of thiamin to the diet in 2 out of 3 mice

hematopoietic system

abnormal definitive hematopoiesis ( J:79974 )

• dysplastic hematopoiesis and reversed myeloid to erythroid ratio

abnormal erythropoiesis ( J:79974 )

• dyssynchrony of nuclear and cytoplasmic maturation

• increase in early erythroid precursors and oversized cells at all stages

abnormal myelopoiesis ( J:79974 )

• larger cells

• increased lobulation of megakaryocyte nuclei

homeostasis/metabolism

decreased circulating insulin level ( J:79974 )

• impaired insulin secretion with thiamin deficiency

impaired glucose tolerance ( J:79974 )

• blood glucose still elevated 120 min into test

• after 17 days without dietary thiamin, glucose intolerant as determined in a glucose tolerance test

• glucose intolerance is resolved 6 weeks after reintroduction of thiamin to diet

increased insulin sensitivity ( J:79974 )

• prolonged hypoglycemic response in an insulin tolerance

immune system

abnormal myelopoiesis ( J:79974 )

• larger cells

• increased lobulation of megakaryocyte nuclei

endocrine/exocrine glands

decreased testis weight ( J:87410 )

♂ • half normal weight

♂ • many apoptotic cells in the tubules

digestive/alimentary system

digestive/alimentary phenotype ( J:170952 )

N • thiamin uptake is normal

Mouse Models of Human Disease		DO ID	OMIM ID(s)	Ref(s)
thiamine-responsive megaloblastic anemia syndrome		DOID:0090117	OMIM:249270	J:79974