B6.Cg-Slc2a9^tm1.1Thor Alb^{tm1(cre/ERT2)Mtz}/ThorOrl

Status	Available to order
EMMA ID	EM:12351
International strain name	B6.Cg-Slc2a9^tm1.1Thor Alb^{tm1(cre/ERT2)Mtz}/ThorOrl
Alternative name	B6-Albtm1(creERT2)Pch Slc2a9tm(lox/lox)Thor
Strain type	Targeted Mutant Strains : Conditional mutation
Allele/Transgene symbol	Slc2a9^tm1.1Thor, Alb^{tm1(cre/ERT2)Mtz}
Gene/Transgene symbol	Slc2a9, Alb

Information from provider

Provider	Bernard Thorens
Provider affiliation	Faculty of Biology and Medicine Center for Integrative Genomics, Universite de Lausanne
Genetic information	Full-body conditional knock-out. Exon 4 of Slc2a9 gene was flanked by two loxP sites (Preitner et al. PNAS 2009 Sep 8;106(36):15501-6), allowing its liver-specific and tamoxifen-inducible excision by cre recombinase when Slc2a9 mice are crossed with Alb-creERT2 mice (Schuler M, et al. Genesis. 2004; 39: 167-72). Generation of the liver-specific Slc2a9 knockout mice is described in detail in Preitner et al. PNAS 2009 Sep 8;106(36):15501-6. Producer: Pr Bernard Thorens, UniL, CIG, Lausanne Method of production: Cross-breeding between parental lines (Female: B6-Albtm1(creERT2)Pch; Male: B6-Slc2a9tm(lox/lox)Thor) generates AlbCre(ERT2)-Slc2a9lox/+ mice. These are further crossed with Slc2a9 breeder to generate Slc2a9 lox/lox (controls) and Alb-cre(ERT2)-Slc2a9 lox/lox (inducible mutants). Experimental cohorts are obtained by breeding controls x mutants, yielding 50% of each genotype (control and mutant), i.e. 100% breeding efficacy.
Phenotypic information	Homozygous: The LG9 knockout mice (Alb-creERT2;Glut9loxlox) show mild hyperuricemia (120umol/l). No phenotype before tamoxifen-induced gene deletion in Alb-creERT2;Slc2a9lox/lox mice. Mild hyperuricemia after tamoxifen induction, associated with a very mild increase in water intake (+20%) and urine volume, without any observed consequence on the housing requirements (drinking control, cage change), general behaviour, metabolic health (energy homeostasis, glucose homeostasis, blood pressure). No development of any complication with age. Degree of severity assessed retrospectively on more than 100 tamoxifen-induced mice: 0 The Alb-creERT2 transgene allows the tamoxifen-inducible expression of cre recombinase. The Slc2a9 mutation is recessive, as indicated by the absence of phenotype in heterozygous mice. Heterozygous: None
Breeding history	Started in 2012; 8 generations.
References	Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy.;Preitner Frédéric, Bonny Olivier, Laverrière Alexandra, Rotman Samuel, Firsov Dmitri, Da Costa Anabela, Metref Salima, Thorens Bernard, ;2009;Proceedings of the National Academy of Sciences of the United States of America;106;15501-6; 19706426 No development of hypertension in the hyperuricemic liver-Glut9 knockout mouse.;Preitner Frederic, Pimentel Anabela, Metref Salima, Berthonneche Corinne, Sarre Alexandre, Moret Catherine, Rotman Samuel, Centeno Gabriel, Firsov Dmitri, Thorens Bernard, ;2015;Kidney international;87;940-7; 25565311 Urate-induced acute renal failure and chronic inflammation in liver-specific Glut9 knockout mice.;Preitner Frederic, Laverriere-Loss Alexandra, Metref Salima, Da Costa Anabela, Moret Catherine, Rotman Samuel, Bazin Dominique, Daudon Michel, Sandt Christophe, Dessombz Arnaud, Thorens Bernard, ;2013;American journal of physiology. Renal physiology;305;F786-95; 23804456
Homozygous fertile	not known
Homozygous viable	yes
Homozygous matings required	no
Immunocompromised	no

Information from EMMA

Archiving centre	Institut de Transgenose, INTRAGENE, Orléans, France
Animals used for archiving	heterozygous C57BL/6J

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

Hereditary renal hypouricemia / Orphanet_94088
Congenital analbuminemia / Orphanet_86816

MGI phenotypes (gene matching)

decreased circulating calcium level / MGI
no abnormal phenotype detected / MGI
decreased circulating serum albumin level / MGI
mortality/aging / MGI
increased alkaline phosphatase activity / MGI
hydronephrosis / MGI
kidney cortex cysts / MGI
decreased body weight / MGI
polydipsia / MGI
polyuria / MGI
kidney inflammation / MGI
no abnormal phenotype detected / MGI
dilated renal tubules / MGI
nephrolithiasis / MGI
decreased urine osmolality / MGI
renal interstitial fibrosis / MGI
increased circulating creatinine level / MGI
increased urine potassium level / MGI
increased urine sodium level / MGI
increased blood uric acid level / MGI
decreased urine pH / MGI
increased circulating magnesium level / MGI
abnormal renal reabsorbtion / MGI
prenatal lethality, incomplete penetrance / MGI
renal tubule atrophy / MGI
tubulointerstitial nephritis / MGI
kidney cortex atrophy / MGI
increased urine magnesium level / MGI
uraturia / MGI

Literature references

Glut9 is a major regulator of urate homeostasis and its genetic inactivation induces hyperuricosuria and urate nephropathy.;Preitner Frédéric, Bonny Olivier, Laverrière Alexandra, Rotman Samuel, Firsov Dmitri, Da Costa Anabela, Metref Salima, Thorens Bernard, ;2009;Proceedings of the National Academy of Sciences of the United States of America;106;15501-6; 19706426
No development of hypertension in the hyperuricemic liver-Glut9 knockout mouse.;Preitner Frederic, Pimentel Anabela, Metref Salima, Berthonneche Corinne, Sarre Alexandre, Moret Catherine, Rotman Samuel, Centeno Gabriel, Firsov Dmitri, Thorens Bernard, ;2015;Kidney international;87;940-7; 25565311
Urate-induced acute renal failure and chronic inflammation in liver-specific Glut9 knockout mice.;Preitner Frederic, Laverriere-Loss Alexandra, Metref Salima, Da Costa Anabela, Moret Catherine, Rotman Samuel, Bazin Dominique, Daudon Michel, Sandt Christophe, Dessombz Arnaud, Thorens Bernard, ;2013;American journal of physiology. Renal physiology;305;F786-95; 23804456

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Availabilities

Requesting frozen sperm or embryos is generally advisable wherever possible, in order to minimise the shipment of live mice.

Frozen sperm. Delivered in 4 weeks (after paperwork in place). €1740^*
Rederivation of mice from frozen stock, delivery time available upon request . €3880^*

Due to the dynamic nature of our processes strain availability may change at short notice. The local repository manager will advise you in these circumstances.

^* In addition users have to cover all the shipping costs (including the cost for returning dry-shippers, where applicable).

More details on pricing and delivery times

Practical information

Genotyping protocol

Example health report
(Current health report will be provided later)

Material Transfer Agreement (MTA)
Distribution of this strain is subject to a provider MTA. Both signing of the MTA and submission of the online EMMA Mutant Request Form are required before material can be shipped.

EMMA conditions
Legally binding conditions for the transfer

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B6.Cg-Slc2a9tm1.1Thor Albtm1(cre/ERT2)Mtz/ThorOrl