Table 1.
Overview of key findings of genetically engineered mouse models.
| Mouse model | Metabolic phenotype | Reproductive phenotype | Reference |
|---|---|---|---|
| Leptin | |||
| Leptin deficiency (ob/ob) & Leptin receptor deficiency (db/db) | Obese Diabetic | Infertile | (for a comprehensive review (Elias and Purohit, 2013) |
| Leptin Circuitry | |||
| Neuron-specific deletion of LepR | Obese Diabetic | ? | (McMinn et al., 2004) |
| Neuron-specific recovery of LepRb | Leaner | Improved fertility | (Kowalski et al., 2001) |
| GnRH specific deletion of LepRb | None | None | (Quennell et al., 2009) |
| Deletion of LepRb in Kiss-1 cells | None | None | (Donato et al., 2011) |
| Re-expression of LepRb in Kiss-1 cells | Obese | Infertile | (Cravo et al., 2013) |
| Re-expression of LepRb specifically in the PMv | Obese | Improved fertility | (Donato et al., 2011) |
| Ablation of AgRP neurons in ob/ob | Lean | Improved fertility | (Wu et al., 2012) |
| Deletion of LepRb in vGluT2 cells | None | None | (Kong et al., 2012; Zuure et al., 2013) |
| Deletion of LepRb in Vgat cells | Obese | Delay in puberty Prolonged estrous cycles | (Zuure et al., 2013) |
| Leptin Signaling | |||
| Deletion of STAT5 in LepRb cells | None | None | (Singireddy et al., 2013) |
| Deletion of STAT3 in LepRb cells | Obese | Fertile | (Singireddy et al., 2013) |
| Point mutation in LepRb STAT3 signaling Tyr1138→ S1138 | Obese | Fertile | (Bates et al., 2003) |
| Point mutation LepRb ERK signaling Tyr985→ L985 | Lean | Fertile | (Bjornholm et al., 2007) |
| Point mutation LepRb STAT5 signaling Tyr1077 → F1077 | Mild increase in adiposity | Slightly lengthened estrous cycle | (Patterson et al., 2012) |
| Global deletion of Crtc1 | Increased body weight | Infertile or None | (Altarejos et al., 2008; Breuillaud et al., 2009) |
| Insulin | |||
| Neuron specific deletion of IR | Increased body weight | Impaired fertility | (Bruning et al., 2000) |
| Global IRS2 deletion | Increased circulating leptin | Low gonadotropin secretion | (Burks et al., 2000) |
| Global deletion of p110α | Heterozygotes leaner | Heterozygotes fertile | (Foukas et al., 2006) |
| GnRH specific deletion of IR | None | None | (Divall et al., 2010) |
| Deletion of IR in Kiss-1 cells | None | Slight delay in pubertal onset | (Qiu et al., 2013) |
| Deletion of IR in POMC cells | None | None | (Hill et al., 2010) |
| Double deletion of IR and LepRb in POMC cells | Insulin resistance | Impairments in fertility Hyperandrogenemia | (Hill et al., 2010) |
| Deletion of IRS2 in LepRb cells | Increased body weight | None | (Sadagurski et al., 2012) |
| Ghrelin | |||
| Global GHSR KO | Resistant to high fat diet | ? | (Zigman et al., 2005) |