Phenotypes associated with this allele

• Allele Symbol: Gpr142^tm1Lex
• Allele Name: targeted mutation 1, Lexicon Genetics
• Allele ID: MGI:3529039
• Summary: 1 genotype

Jump to	Allelic Composition	Genetic Background	Genotype ID
hm1	Gpr142^tm1Lex/Gpr142^tm1Lex	B6.129S-Gpr142^tm1Lex	MGI:6515590

Genotype
MGI:6515590

hm1

• Allelic Composition: Gpr142^tm1Lex/Gpr142^tm1Lex
• Genetic Background: B6.129S-Gpr142^tm1Lex

• ♀: phenotype observed in females
• ♂: phenotype observed in males
• N: normal phenotype

homeostasis/metabolism

decreased insulin secretion ( J:249154 )

• in vitro, isolated pancreatic islets incubated at 11.1mM glucose in the presence of varying concentrations of L-Tryptophan (L-Trp) exhibit significantly lower insulin concentrations in the culture media than similarly treated wild-type islets

• however, pancreatic islets show normal insulin secretory capacity under low glucose or high glucose conditions without exogenous amino acid treatment, as well as normal insulin release in the presence of varying concentrations of L-Phenylalanine (L-Phe) or upon stimulation with either Exendin-4 (a GLP-1 receptor agonist) or L-Arginine

abnormal circulating glucose level ( J:249154 )

• oral dosing of L-Trp fails to suppress glucose excursion during an intraperitoneal glucose tolerance test (IPGTT) and oral glucose tolerance test (OGTT), unlike in wild-type controls

• similarly, oral dosing of compound A (a synthetic GPR142 agonist) fails to suppress glucose excursion during an IPGTT, unlike in wild-type controls

• however, the glucose-lowering effect of L-Phe during IPGTT is still intact, as in wild-type controls

• after refeeding, blood glucose levels are not significantly different from those in refed wild-type controls

increased fasting circulating glucose level ( J:249154 )

• in response to a high-fat diet (HFD), mice show a ~20 mg/dL increase in fasting glycemia during an OGTT, with no significant change in plasma insulin levels

• however, HFD-fed mice show no significant changes in body weight, food intake, and ad libitum fed blood glucose or plasma insulin levels

abnormal circulating hormone level ( J:249154 )

• in vivo, no L-Trp-dependent release of glucose-dependent insulinotropic polypeptide (GIP) is observed 10 minutes after oral dosing as determined by plasma GIP levels; in contrast, oral dosing of L-Trp rapidly and dose-dependently increases plasma GIP levels in wild-type controls, reaching peak concentrations at 5-10 minutes after dosing

• L-Phe-induced GIP release is blunted, as determined by plasma GIP levels at 10 minutes after oral dosing

• compound A (a synthetic GPR142 agonist)-induced release of GIP or glucagon-like peptide-1 (GLP-1) is absent, as determined, respectively, by plasma GIP or GLP-1 levels at 30 minutes after oral dosing

• at 30, but not 90, minutes after refeeding, plasma GIP levels are significantly blunted relative to those in refed wild-type controls

• both L-Trp and L-Phe increase plasma GLP-1 levels to a similar extent as in wild-type mice

• after refeeding, plasma GLP-1 levels are not significantly different from those in refed wild-type controls

abnormal circulating insulin level ( J:249154 )

• in vivo, no L-Trp-dependent release of insulin is observed 10 minutes after oral dosing as determined by plasma insulin levels; in contrast, oral dosing of L-Trp rapidly and dose-dependently increases plasma insulin levels in wild-type controls reaching peak concentrations at 5-10 minutes after dosing

• L-Phe-induced insulin release is blunted, as determined by plasma insulin levels at 10 minutes after oral dosing

• compound A (a synthetic GPR142 agonist)-induced insulin release is absent, as determined by plasma insulin levels at 30 minutes after oral dosing

decreased circulating insulin level ( J:249154 )

• at 30, but not 90, minutes after refeeding, plasma insulin levels are significantly blunted relative to those in refed wild-type controls

abnormal circulating non-HDL cholesterol level ( J:249154 )

• in response to a HFD, mice show a 50% increase in plasma non-HDL cholesterol levels relative to wild-type controls

endocrine/exocrine glands

decreased insulin secretion ( J:249154 )

• in vitro, isolated pancreatic islets incubated at 11.1mM glucose in the presence of varying concentrations of L-Tryptophan (L-Trp) exhibit significantly lower insulin concentrations in the culture media than similarly treated wild-type islets

• however, pancreatic islets show normal insulin secretory capacity under low glucose or high glucose conditions without exogenous amino acid treatment, as well as normal insulin release in the presence of varying concentrations of L-Phenylalanine (L-Phe) or upon stimulation with either Exendin-4 (a GLP-1 receptor agonist) or L-Arginine

digestive/alimentary system

digestive/alimentary phenotype ( J:249154 )

N • mice show normal increases in plasma levels of GIP and total GLP-1 after glucose oral dosing, suggesting normal enteroendocrine K- and L-cell function