C;129P2-Thra^tm2Ven/Kctt

Status	Available to order
EMMA ID	EM:04560
International strain name	C;129P2-Thra^tm2Ven/Kctt
Alternative name	Thra-tm2Ven
Strain type	Targeted Mutant Strains : Knock-out
Allele/Transgene symbol	Thra^tm2Ven
Gene/Transgene symbol	Thra

Information from provider

Provider	Björn Vennström
Provider affiliation	Department of Cell and Molecular Biology, Karolinska Institutet, CMB
Genetic information	The RNAs for the thyroid hormone receptor alpha (Thra) TRa1 and TRa2 isoforms appear to be produced by a use of alternative transcriptional stops and subsequent splicing. Expression of the TRa2 isoform of the thyroid hormone receptor was completely abolished by abrogating transcription into exon 10, i.e. the exon that encodes the TRa2-specific coding sequence. As a result, all RNAs transcribed from the Thra locus by default encode the TRa1 isoform, and at elevated levels. Both RNA and protein levels for TRa1 are increased approx. 6-fold in the homozygote, 3-fold in the heterozygote. The artificial transcriptional stop is provided by the inserted neomycin-resistance cassette.
Phenotypic information	Analysis of the phenotype revealed a mixed hypo- and hyperthyroid phenotype in both the homo- and heterozygotes. These features include moderately reduced levels of serum thyroid hormones, an increased heart rate, elevated body temperature and delayed ossification. These characteristics were ascribed to the elevated expression of TRa1, whereas no phenotype could be associated with the lack of TRa2 expression (Salto et al., 2001). The elevated expression of TRa1 can substitute for Thr-beta in Thrb-/- mice (Ng et al., 2001).
Breeding history	The founders were backcrossed for approx 4 generations against BALB/c. The strain has been maintained as a heterozygote.
References	Ablation of TRalpha2 and a concomitant overexpression of alpha1 yields a mixed hypo- and hyperthyroid phenotype in mice.;Saltó C, Kindblom J M, Johansson C, Wang Z, Gullberg H, Nordström K, Mansén A, Ohlsson C, Thorén P, Forrest D, Vennström B, ;2001;Molecular endocrinology (Baltimore, Md.);15;2115-28; 11731613 A thyroid hormone receptor that is required for the development of green cone photoreceptors.;Ng L, Hurley J B, Dierks B, Srinivas M, Saltó C, Vennström B, Reh T A, Forrest D, ;2001;Nature genetics;27;94-8; 11138006
Homozygous fertile	yes
Homozygous viable	yes
Homozygous matings required	no
Immunocompromised	not known

Information from EMMA

Archiving centre	Karolinska Institutet, Stockholm, Sweden

Disease and phenotype information

Orphanet associated rare diseases, based on orthologous gene matching

Resistance to thyroid hormone due to a mutation in thyroid hormone receptor alpha / Orphanet_566231

IMPC phenotypes (gene matching)

hyperactivity / IMPC
increased vertical activity / IMPC
increased startle reflex / IMPC
improved glucose tolerance / IMPC
abnormal retina inner nuclear layer morphology / IMPC
decreased startle reflex / IMPC
increased circulating creatinine level / IMPC
decreased total retina thickness / IMPC
abnormal contextual conditioning behavior / IMPC
short tibia / IMPC
increased bone mineral content / IMPC
abnormal heart left ventricle morphology / IMPC
limb grasping / IMPC
preweaning lethality, incomplete penetrance / IMPC
increased bone mineral density / IMPC
decreased body length / IMPC
decreased total body fat amount / IMPC
increased blood urea nitrogen level / IMPC
abnormal bone structure / IMPC
increased hematocrit / IMPC
decreased grip strength / IMPC
increased circulating alkaline phosphatase level / IMPC
decreased exploration in new environment / IMPC

MGI phenotypes (allele matching)

decreased bone mineral density / MGI
abnormal trabecular bone morphology / MGI
obese / MGI
decreased body weight / MGI
postnatal growth retardation / MGI
increased heart rate / MGI
abnormal thyroid physiology / MGI
increased activity of thyroid / MGI
decreased activity of thyroid / MGI
abnormal compact bone morphology / MGI
abnormal thyroid-stimulating hormone level / MGI
decreased circulating insulin-like growth factor I level / MGI
decreased circulating thyroxine level / MGI
decreased circulating triiodothyronine level / MGI
increased body temperature / MGI
increased total body fat amount / MGI
decreased compact bone area / MGI
abnormal pup retrieval / MGI
abnormal osteoclast physiology / MGI
reduced female fertility / MGI
abnormal thyroid follicle morphology / MGI
prolonged estrous cycle / MGI
decreased bone mineral content / MGI
perinatal lethality, incomplete penetrance / MGI
decreased areal bone mineral density / MGI
hearing/vestibular/ear phenotype / MGI

MGI phenotypes (gene matching)

decreased bone mineral density / MGI
abnormal trabecular bone morphology / MGI
abnormal long bone metaphysis morphology / MGI
decreased compact bone thickness / MGI
delayed hair appearance / MGI
abnormal enterocyte morphology / MGI
abnormal small intestine morphology / MGI
abnormal intestinal mucosa morphology / MGI
short limbs / MGI
short tail / MGI
abnormal hippocampus morphology / MGI
abnormal cerebellum external granule cell layer morphology / MGI
decreased body length / MGI
increased body weight / MGI
obese / MGI
decreased body weight / MGI
increased anxiety-related response / MGI
abnormal pup retrieval / MGI
abnormal object recognition memory / MGI
abnormal osteoclast physiology / MGI
abnormal bone strength / MGI
abnormal postnatal growth / MGI
postnatal growth retardation / MGI
reduced fertility / MGI
reduced male fertility / MGI
reduced female fertility / MGI
decreased litter size / MGI
abnormal glucose homeostasis / MGI
increased circulating insulin level / MGI
premature death / MGI
small heart / MGI
increased heart rate / MGI
increased glucagon secretion / MGI
increased circulating glucagon level / MGI
short tibia / MGI
abnormal thyroid physiology / MGI
increased insulin sensitivity / MGI
abnormal bone mineralization / MGI
abnormal joint morphology / MGI
abnormal bone remodeling / MGI
abnormal long bone epiphyseal plate morphology / MGI
increased insulin secretion / MGI
prolonged QT interval / MGI
abnormal locomotor coordination / MGI
decreased liver weight / MGI
decreased width of hypertrophic chondrocyte zone / MGI
delayed endochondral bone ossification / MGI
delayed intramembranous bone ossification / MGI
abnormal intestinal goblet cell morphology / MGI
thyroid hypoplasia / MGI
increased activity of thyroid / MGI
decreased activity of thyroid / MGI
abnormal insulin secretion / MGI
oliguria / MGI
abnormal response/metabolism to endogenous compounds / MGI
abnormal long bone epiphyseal plate proliferative zone / MGI
abnormal bone structure / MGI
abnormal compact bone morphology / MGI
abnormal defecation / MGI
abnormal hormone level / MGI
abnormal thyroid-stimulating hormone level / MGI
increased compact bone thickness / MGI
abnormal long bone diaphysis morphology / MGI
short ulna / MGI
abnormal cochlear outer hair cell morphology / MGI
decreased length of long bones / MGI
abnormal thyroid follicle morphology / MGI
decreased circulating insulin-like growth factor I level / MGI
decreased mean systemic arterial blood pressure / MGI
decreased osteoclast cell number / MGI
decreased bone resorption / MGI
increased circulating thyroid-stimulating hormone level / MGI
increased thyroid-stimulating hormone level / MGI
abnormal pancreatic islet morphology / MGI
impaired glucose tolerance / MGI
insulin resistance / MGI
decreased heart rate / MGI
hearing/vestibular/ear phenotype / MGI
behavior/neurological phenotype / MGI
skeleton phenotype / MGI
osteosclerosis / MGI
increased triiodothyronine level / MGI
increased circulating thyroxine level / MGI
decreased circulating thyroxine level / MGI
decreased circulating triiodothyronine level / MGI
increased circulating triiodothyronine level / MGI
increased body temperature / MGI
decreased body temperature / MGI
increased circulating glucose level / MGI
abnormal enzyme/coenzyme activity / MGI
decreased ventricle muscle contractility / MGI
increased bone mass / MGI
increased circulating leptin level / MGI
increased long bone epiphyseal plate size / MGI
abnormal long bone epiphyseal ossification zone morphology / MGI
impaired lipolysis / MGI
increased diameter of long bones / MGI
abnormal enterocyte physiology / MGI
abnormal enterocyte proliferation / MGI
prolonged estrous cycle / MGI
small pancreatic islets / MGI
increased epididymal fat pad weight / MGI
increased trabecular bone thickness / MGI
abnormal chondrocyte physiology / MGI
increased total body fat amount / MGI
abnormal bone mineral content / MGI
increased bone mineral content / MGI
decreased bone mineral content / MGI
prolonged QRS complex duration / MGI
delayed cranial suture closure / MGI
increased bone trabecula number / MGI
increased trabecular bone volume / MGI
abnormal mitochondrial ATP synthesis coupled electron transport / MGI
increased compact bone volume / MGI
decreased compact bone area / MGI
decreased core body temperature / MGI
impaired adaptive thermogenesis / MGI
postnatal lethality, complete penetrance / MGI
perinatal lethality, incomplete penetrance / MGI
prenatal lethality, complete penetrance / MGI
decreased food intake / MGI
decreased areal bone mineral density / MGI
decreased small intestine length / MGI
decreased small intestinal villus height / MGI
decreased cardiac cell glucose uptake / MGI
wide cranial sutures / MGI
large fontanelles / MGI

Literature references

Ablation of TRalpha2 and a concomitant overexpression of alpha1 yields a mixed hypo- and hyperthyroid phenotype in mice.;Saltó C, Kindblom J M, Johansson C, Wang Z, Gullberg H, Nordström K, Mansén A, Ohlsson C, Thorén P, Forrest D, Vennström B, ;2001;Molecular endocrinology (Baltimore, Md.);15;2115-28; 11731613
A thyroid hormone receptor that is required for the development of green cone photoreceptors.;Ng L, Hurley J B, Dierks B, Srinivas M, Saltó C, Vennström B, Reh T A, Forrest D, ;2001;Nature genetics;27;94-8; 11138006

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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).

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C;129P2-Thratm2Ven/Kctt