RGD Reference Report - Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Koletsky obese rat. - Rat Genome Database

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Phenotype of the obese Koletsky (f) rat due to Tyr763Stop mutation in the extracellular domain of the leptin receptor (Lepr): evidence for deficient plasma-to-CSF transport of leptin in both the Zucker and Koletsky obese rat.

Authors: Wu-Peng, XS  Chua SC, JR  Okada, N  Liu, SM  Nicolson, M  Leibel, RL 
Citation: Wu-Peng XS, etal., Diabetes. 1997 Mar;46(3):513-8.
RGD ID: 11570540
Pubmed: PMID:9032111   (View Abstract at PubMed)

The obese phenotypes of the diabetes (db) mouse and fatty fa) rat are due to functional null mutations of the leptin receptor (Lepr). The recessive mutation in the Koletsky (f) obese rat maps to the same genetic intervals as db and fa and fails to complement the fa mutation. Comparison of the sequence of brain Lepr cDNA from +/+ and f/f animals reveals a T2349A transversion resulting in a Tyr763Stop nonsense mutation in the gene just before the transmembrane domain. Virtual absence of Lepr mRNA in whole brain from f/f animals is consistent with the presence of a null mutation. The predicted reduced cerebrospinal fluid (CSF) transport of leptin in both f/f and fa/fa mutants is reflected in the approximately 10-fold lower ratio of CSF/plasma leptin concentration in the obese versus lean animals. However, equivalent CSF leptin concentration between lean and obese rats (fa/fa, f/f) indicates that leptin can enter the CSF through a non-Lepr-mediated mechanism, which may be saturated at normal physiological plasma leptin concentration.



Phenotype Annotations    Click to see Annotation Detail View

Mammalian Phenotype

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BN.ZUC-LeprfaRatincreased body mass index  IAGP compared to lean littermatesRGD 
LA-cp/NRllRatincreased body mass index  IAGP compared to lean littermatesRGD 
LeprRatincreased body mass index  IAGP compared to lean littermatesRGD 
LeprcpRatincreased body mass index  IAGP compared to lean littermatesRGD 
LeprfaRatincreased body mass index  IAGP compared to lean littermatesRGD 
BN.ZUC-LeprfaRatincreased circulating leptin level  IAGP compared to lean littermatesRGD 
LA-cp/NRllRatincreased circulating leptin level  IAGP compared to lean littermatesRGD 
LeprRatincreased circulating leptin level  IAGP compared to lean littermatesRGD 
LeprcpRatincreased circulating leptin level  IAGP compared to lean littermatesRGD 
LeprfaRatincreased circulating leptin level  IAGP compared to lean littermatesRGD 
Objects Annotated

Genes (Rattus norvegicus)
Lepr  (leptin receptor)
Leprcp  (leptin receptor;corpulent)
Leprfa  (leptin receptor; fa mutant)

Strains
BN.ZUC-Leprfa  (NA)
LA-cp/NRll  (NA)


Additional Information