B6.129-Ppargc1b^tm1.1Avp/Kctt

Status	Available to order
EMMA ID	EM:04679
International strain name	B6.129-Ppargc1b^tm1.1Avp/Kctt
Alternative name	B6.129-Ppargc1b tm1AZTC
Strain type	Targeted Mutant Strains : Knock-out
Allele/Transgene symbol	Ppargc1b^tm1.1Avp,
Gene/Transgene symbol	Ppargc1b

Information from provider

Provider	Mohammad Bohlooly
Provider affiliation	ATCG, AstraZeneca R&D
Genetic information	A triple loxP strategy was used to target the PGC-1b (Ppargc1b) locus to generate mice with both standard and conditional knock-out alleles at this locus. The homology region used in the targeting vector was amplified by proof-reading PCR using a 129/SvJ genomic RPCI Mouse PAC clone as a template. In essence, the targeting vector was a ~8kb 129/SvJ mouse genomic subclone containing a floxed neomycin phosphotransferase selectable marker cassette inserted into intron 3 and a single loxP site inserted into intron 5.
Phenotypic information	PGC-1beta (Ppargc1b) knock-out mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1beta ablation was partially compensated by up-regulation of PGC-1alpha in BAT and white adipose tissue (WAT) that led to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC-1beta knock-out mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1beta was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC-1beta knock-out hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC-1beta knock-out mice have impaired mitochondrial function. Lack of PGC-1beta also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1beta plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses.
Breeding history	The strain is bred on C57BL/6 in a het x wt colony.
References	PGC-1beta: a co-activator that sets the tone for both basal and stress-stimulated mitochondrial activity.;Lelliott Christopher J, Vidal-Puig Antonio, ;2009;Advances in experimental medicine and biology;646;133-9; 19536672 Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance.;Lelliott Christopher J, Medina-Gomez Gema, Petrovic Natasa, Kis Adrienn, Feldmann Helena M, Bjursell Mikael, Parker Nadeene, Curtis Keira, Campbell Mark, Hu Ping, Zhang Dongfang, Litwin Sheldon E, Zaha Vlad G, Fountain Kimberly T, Boudina Sihem, Jimenez-Linan Mercedes, Blount Margaret, Lopez Miguel, Meirhaeghe Aline, Bohlooly-Y Mohammad, Storlien Leonard, Strömstedt Maria, Snaith Michael, Oresic Matej, Abel E Dale, Cannon Barbara, Vidal-Puig Antonio, ;2006;PLoS biology;4;e369; 17090215
Homozygous fertile	yes
Homozygous viable	yes
Homozygous matings required	no
Immunocompromised	no

Information from EMMA

Archiving centre	Karolinska Institutet, Stockholm, Sweden

Disease and phenotype information

MGI phenotypes (allele matching)

decreased body weight / MGI
decreased white adipose tissue amount / MGI
hepatic steatosis / MGI
decreased circulating triglyceride level / MGI
abnormal white adipose tissue morphology / MGI
increased liver weight / MGI
decreased circulating cholesterol level / MGI
abnormal metabolism / MGI
decreased oxygen consumption / MGI
decreased heart rate / MGI
abnormal mitochondrion morphology / MGI
increased white fat cell size / MGI
decreased gonadal fat pad weight / MGI

Literature references

PGC-1beta: a co-activator that sets the tone for both basal and stress-stimulated mitochondrial activity.;Lelliott Christopher J, Vidal-Puig Antonio, ;2009;Advances in experimental medicine and biology;646;133-9; 19536672
Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance.;Lelliott Christopher J, Medina-Gomez Gema, Petrovic Natasa, Kis Adrienn, Feldmann Helena M, Bjursell Mikael, Parker Nadeene, Curtis Keira, Campbell Mark, Hu Ping, Zhang Dongfang, Litwin Sheldon E, Zaha Vlad G, Fountain Kimberly T, Boudina Sihem, Jimenez-Linan Mercedes, Blount Margaret, Lopez Miguel, Meirhaeghe Aline, Bohlooly-Y Mohammad, Storlien Leonard, Strömstedt Maria, Snaith Michael, Oresic Matej, Abel E Dale, Cannon Barbara, Vidal-Puig Antonio, ;2006;PLoS biology;4;e369; 17090215

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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 embryos. 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

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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B6.129-Ppargc1btm1.1Avp/Kctt