Overview

This THTR-2^- knockout mouse line has a deletion of exons 1-2 of the Slc19a3 gene. These mice may be useful in studying the role of thiamin transporters in regulating thiamin homeostasis in different cells; including liver and kidney cells.

Donating Investigator

Hamid M Said, University of California, Irvine

Genetic overview

Genetic Background	Generation

Slc19a3^tm1Said

Allele Type	Gene Symbol	Gene Name
Targeted (Null/Knockout)	Slc19a3	solute carrier family 19, member 3

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Research Applications

Research Tools
Cardiovascular Research
Metabolism Research
Internal/Organ Research
Endocrine Deficiency Research
Cell Biology Research
Neurobiology Research

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Base Price

Starting at:

$2,854.50 Domestic price Cryo Recovery

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Details

Detailed Description

The THTR-2^- knockout mutation has exons 1-2 of the thiamin transporter-2 gene (ThTr2 or Slc19a3) replaced by a neo cassette. No mRNA or protein expression is observed in intestinal tissues. Homozygous mice (THTR-2^-/-) are viable and fertile as younger mice. THTR-2^-/- mice exhibit significant decreases in both intestinal thiamin uptake and plasma thiamin levels. No changes in blood biotin, glucose, or insulin levels are reported for homozygotes. The expression of thiamin transporter-1 (THTR-1) is normal in intestine, but increased in kidney, in THTR-2-deficient mice. Homozygotes become lethargic around nine months of age, with cachexia/progressive wasting and eventually premature death by ~12 months of age. Histologic examination at nine months of age reveals increased incidence of both liver defects (hepatic parenchyma injury, necrosis, and chronic inflammation) and kidney defects (interstitial chronic inflammation of the renal cortex, degeneration of the proximal convoluted tubules, and arteriosclerosis/renal nephosclerosis).

Development

A targeting vector was designed to replace exons 1-2 (including the ATG transcriptional start site) of the thiamin transporter-2 gene (ThTr2 or Slc19a3) with a neomycin cassette. The construct was electroporated into undisclosed embryonic stem (ES) cells. Correctly targeted ES cells were injected into recipient blastocysts and chimeric animals were bred with C57BL/6J mice to establish the colony. Mice heterozygous for the THTR-2^- allele were then bred together for several generations (always with black coat color) prior to sending to The Jackson Laboratory Repository. Upon arrival, mice were bred to C57BL/6J (Stock No. 000664) for at least one generation to establish the colony.

Control Suggestions

Wild-type from the colony

Approximate Controls

000664 C57BL/6J

Additional Information

Considerations for Choosing Controls

Selected References

Reidling JC; Lambrecht N; Kassir M; Said HM. 2010. Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice. Gastroenterology 138(5):1802-9PubMed: 19879271 MGI: J:170952

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Genetics

Slc19a3^tm1Said

Allele Symbol: Slc19a3^tm1Said

Allele Name	targeted mutation 1, Hamid M Said
Allele Type	Targeted (Null/Knockout)
Allele Synonym(s)	Slc19a3^tm1Igl; Slc19a3^tm1Itl
Gene Symbol and Name	Slc19a3, solute carrier family 19, member 3
Gene Synonym(s)
Strain of Origin	Not Specified
Chromosome	1
Molecular Note	A neo cassette replaced exons 1 and 2. The absence of protein expression was confirmed by western blot analysis on intestine extracts.
Mutations Made By	Hamid Said, University of California, Irvine

Disease/Phenotype

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

biotin-responsive basal ganglia disease

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Research Tools
- Metabolism Research
Cardiovascular Research
- Metabolic Syndrome
Metabolism Research
Internal/Organ Research
- Liver Defects
- Kidney Defects
  - Renal tubulointerstitial lesions
- Gastrointestinal Defects
Endocrine Deficiency Research
- Kidney Defects
- Gastrointestinal Defects
Cell Biology Research
- Channel and Transporter Defects
Neurobiology Research
- Channel and Transporter Defects
- Metabolic Defects

Mammalian Phenotype Terms by Genotype

The following phenotype information is associated with a similar, but not exact match to this JAX^® Mice strain

Genotype: Slc19a3^tm1Said/Slc19a3^tm1Said
involves: C57BL/6

behavior/neurological phenotype

lethargy
- 2 to 3 months before death

mortality/aging

premature death
- mice die within 1 year of age

renal/urinary system phenotype

abnormal proximal convoluted tubule morphology
- mice exhibit degeneration of the proximal convoluted tubules and arteriolosclerosis compared with wild-type mice

kidney inflammation
- chronic interstitial

nephrosclerosis

cellular phenotype

hepatic necrosis

digestive/alimentary phenotype

abnormal vitamin absorption
- mice exhibit decreased thiamin uptake compared with wild-type mice

growth/size/body region phenotype

cachexia
- 2 to 3 months before death

homeostasis/metabolism phenotype

abnormal thiamin level
- thiamin serum levels are decreased compared to in wild-type mice

abnormal vitamin absorption
- mice exhibit decreased thiamin uptake compared with wild-type mice

immune system phenotype

kidney inflammation
- chronic interstitial

liver inflammation
- chronic

liver/biliary system phenotype

abnormal liver parenchyma morphology
- 4 of 5 mice exhibit hepatic parenchyma injury with necrosis and chronic inflammation in zone 2 (midzonal) and focally extending periportally into zone 1 unlike wild-type mice

hepatic necrosis

liver inflammation
- chronic

Genotype: Slc19a3^tm1Said/Slc19a3^tm1Said
involves: C57BL/6J

behavior/neurological phenotype

abnormal locomotor behavior
- mice fed a thiamine-restricted diet exhibit immobility

paralysis
- mice fed a thiamine-restricted diet exhibit paralysis

nervous system phenotype

astrocytosis
- astrocyte activation is increased in the bilateral thalamic area of mice fed with a thiamine-restricted diet for 12 days

decreased neuron number
- after 12 days of a thiamine-restricted diet, the numbers of NeuN+ neurons are decreased over a wide area of the thalamus, including the submedial nucleus of the thalamus
- after 5 days of a thiamine-restricted diet, the number of NeuN+ neurons in the submedial nucleus of the thalamus and ventral anterior-lateral complex of the thalamus is decreased to approximately 50%

neurodegeneration
- the brains of surviving mice on a high-thiamine diet after 2 days of thiamine restriction show a slight decrease in NeuN+ neurons, no significant astrocyte activation in the thalamus or acute neurodegeneration
- the number of degenerating neurons in the submedial nucleus of the thalamus, ventral anterior-lateral complex of the thalamus and cortex is increased in mice fed a thiamine-restricted diet

homeostasis/metabolism phenotype

abnormal thiamin level
- thiamine concentration in the brain decreases steadily in mice fed a thiamine-restricted diet before mice present disease phenotypes
- thiamine levels in the blood of mice fed a conventional diet are deceased at 7 weeks of age
- thiamine levels in the blood of mice fed a thiamine-restricted diet are decreased

mortality/aging

premature death
- 4 of 7 mice that are returned to a conventional diet after 1 day on a thiamine-restricted diet recover and survive
- mice fed a conventional diet containing 1.71 mg thiamine/100 g of food survive for over 6 months without any disease phenotype
- mice fed a thiamine-restricted diet (0.60 mg thiamine/100 g food) die within 12 days of starting the diet
- mice fed a thiamine-restricted diet with an even lower percentage of thiamine (0.27 mg thiamine/100 g food) die within 14 days
- mice that are returned to a conventional diet after 2 or 3 days on a thiamine-restricted diet, die within the next 24 days
- most mice that are returned to a high-thiamine diet (8.5 mg thiamine/100 g food) after 2, 3, and 5 days of a thiamine-restricted diet are rescued and survive

References

Reidling JC; Lambrecht N; Kassir M; Said HM. 2010. Impaired intestinal vitamin B1 (thiamin) uptake in thiamin transporter-2-deficient mice. Gastroenterology 138(5):1802-9PubMed: 19879271 MGI: J:170952

Additional - Slc19a3^tm1Said related

Technical Support

CONTACT TECHNICAL SUPPORT

Genotyping Protocols
- Separated MCA:Slc19a3
- Separated PCR:Slc19a3
- Genotyping resources and troubleshooting
Breeding Considerations

When maintaining a live colony, heterozygous mice may be bred together or with wildtype mice from the colony. While homozygous mice are viable and fertile as younger mice, they become lethargic around nine months of age, with cachexia/progressive wasting and eventually premature death by ~12 months of age.
- Additional Breeding and Husbandry Support
Citation
When using the STOCK Slc19a3^tm1Said/J mouse strain in a publication, please cite the originating article(s) and include JAX stock #017343 in your Materials and Methods section.

Animal Health Reports

Facility Barrier Level Descriptions

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Pricing & Availability

Cryo Recovery

Domestic
International

Live Mouse

Age

Genotype

Price

weeks

Cryorecovery - Pricing

Service/Product	Description	Price
	Heterozygous or wildtype for Slc19a3<tm1Said>

Related Products and Services

Frozen Mouse Embryo	STOCK Slc19a3<tm1Said>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Slc19a3<tm1Said>/J Frozen Embryo	$2595.00
Frozen Mouse Embryo	STOCK Slc19a3<tm1Said>/J Frozen Embryo	$3373.50
Frozen Mouse Embryo	STOCK Slc19a3<tm1Said>/J Frozen Embryo	$3373.50

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The Jackson Laboratory's Genotype Promise

The Jackson Laboratory has rigorous genetic quality control and mutant gene genotyping programs to ensure the genetic background of JAX® Mice strains as well as the genotypes of strains with identified molecular mutations. JAX® Mice strains are only made available to researchers after meeting our standards. However, the phenotype of each strain may not be fully characterized and/or captured in the strain data sheets. Therefore, we cannot guarantee a strain's phenotype will meet all expectations. To ensure that JAX® Mice will meet the needs of individual research projects or when requesting a strain that is new to your research, we suggest ordering and performing tests on a small number of mice to determine suitability for your particular project. We do not guarantee breeding performance and therefore suggest that investigators order more than one breeding pair to avoid delays in their research.

Terms Of Use

General Terms and Conditions

Questions about Terms of Use

Licensing Information

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JAX® Mice, Products & Services Conditions of Use

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Donating Investigator

Genetic overview

Research Applications

Base Price

Detailed Description

Development

Control Suggestions

Approximate Controls

Additional Information

Selected References

Slc19a3tm1Said

Allele Symbol: Slc19a3tm1Said

Disease Terms

Model with phenotypic similarity to human disease where etiologies involve orthologs. Human genes are associated with this disease. Orthologs of those genes appear in the mouse genotype(s).

Research Areas By Phenotype

This mouse can be used to support research in many areas including:

Mammalian Phenotype Terms by Genotype

Genotype: Slc19a3tm1Said/Slc19a3tm1Saidinvolves: C57BL/6

behavior/neurological phenotype

mortality/aging

renal/urinary system phenotype

cellular phenotype

digestive/alimentary phenotype

growth/size/body region phenotype

homeostasis/metabolism phenotype

immune system phenotype

liver/biliary system phenotype

Genotype: Slc19a3tm1Said/Slc19a3tm1Saidinvolves: C57BL/6J

behavior/neurological phenotype

nervous system phenotype

homeostasis/metabolism phenotype

mortality/aging

References

Additional - Slc19a3tm1Said related

Genotyping Protocols

Breeding Considerations

Citation

Animal Health Reports

Production of mice from cryopreserved embryos or sperm occurs in a maximum barrier room, G200

Live Mouse

Cryorecovery - Pricing

Related Products and Services

Payment Terms and Conditions

The Jackson Laboratory's Genotype Promise

Terms Of Use

Licensing Information

JAX® Mice, Products & Services Conditions of Use

No Warranty

Credit for PRODUCTS or SERVICES

Animal Care and Use for SERVICES

No Liability

Slc19a3^tm1Said

Allele Symbol: Slc19a3^tm1Said

Genotype: Slc19a3^tm1Said/Slc19a3^tm1Said
involves: C57BL/6

Genotype: Slc19a3^tm1Said/Slc19a3^tm1Said
involves: C57BL/6J

Additional - Slc19a3^tm1Said related