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PubMed2004

Developmental contribution of c-maf in the kidney: distribution and developmental study of c-maf mRNA in normal mice kidney and histological study of c-maf knockout mice kidney and liver.

Maf is a family of oncogenes which encodes a nuclear bZip transcription factor protein and has been originally identified from the avian oncogenic retrovirus, AS42. Maf genes have been reported to have critical roles in embryological development and cellular differentiation. In this study, in situ hybridization with (35)S-labeled antisense riboprobes was used to investigate the distribution of c-maf mRNA in balb/c mouse kidneys from 12 (E12) through 17 days (E17) of gestation and then 1 and 4 weeks after birth. Immunocytochemistry of 4-week-old mouse kidney using anti-c-maf antisera was also performed. Kidney and liver sections from c-maf knockout mice at 4 weeks were stained with hematoxylin-eosin, and their histological features were examined. Expression of c-maf mRNA was first detected on E16 in the renal proximal tubules, and it was expressed through 4 weeks after birth. In the c-maf knockout mice at 4 weeks the cytoplasmic volume of the proximal tubule and liver cell was smaller. These findings suggest that expression of the c-maf gene may be involved in the embryological development and/or cell differentiation of kidney and liver cells.

Aging↗

PubMed2004

Oxytocin and estrogen receptor alpha and beta knockout mice provide discriminably different odor cues in behavioral assays.

Social behavior involves both the recognition and pro-duction of social cues. Mice with selective deletion(knockout) of either the gene for oxytocin (OT) or genes for the estrogen receptor (ER) -c or -B display impaired social recognition. In this study we demonstrate that these gene knockout mice also provide discriminably different social stimuli in behavioral assays. In an odor choice test, which is a measure of social interest and discrimination, outbred female Swiss-Webster mice discriminated the urine odors of male knock-outs IKO: OTKO, alphaERKO, betaERKO) from the odors of their wildtype littermates (WT: OTWT, alphaERWT, betaERWT). Females showed marked initial choices of the urine odors of OTWT and betaERWT males over those of OTKOand PERKO males, and alphaERKO males over alphaERWT males. The odors of OTKO and betaERKO males also induced aversive, analgesic responses, with the odors of WTs having no significant effects. Odors of both the alphaERWT andalphaERKO males induced aversive, analgesic responses,with the odors of the WT inducing significantly greater analgesia. The odors of restraint stressed WT and KO males also elicited analgesia with, again, females dis-playing significantly greater responses to the odors of stressed OTKO and betaERKO males than their WTs, and significantly lower analgesia to the odors of stressedalphaERKO than alphaERWT males. These findings show that the KO mice are discriminated from their WTs on the basis of odor and that the various KOs differ in the relative attractiveness/aversiveness of their odors. Therefore, in behavioral assays one causal route by which gene inactivation alters the social behavior of knockout mice may be mediated through the partners'modified responses to their odors.

Animals↗

PubMed1997

The neuronal isoform of constitutive nitric oxide synthase is up-regulated in the macula densa of angiotensinogen gene-knockout mice.

Angiotensinogen gene-knockout (Atg -/-) mice lacking angiotensin II exhibit chronic hypotension and an increase in renal renin gene expression. The present study was designed to provide evidence for the possible involvement of neuronal type nitric oxide synthase (N-NOS) at the macula densa in the increased renin production in Atg -/- mice. The enzyme activity of N-NOS was histochemically detected by NADPH diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. N-NOS mRNA expression in the renal cortical tissue was determined using reverse transcription-PCR in a semiquantitative manner. The levels of renal renin mRNA were evaluated by Northern blot analysis. In the kidneys of wild-type (Atg +/+) mice, N-NOS activity was localized to the macula densa as reported previously. On the other hand, N-NOS-positive macula densa cells of Atg -/- mice were distributed beyond the original location of the macula densa. They often occupy the entire cross-sectional profiles of the tubules. In addition, Atg -/- mice showed a stronger signal intensity for the enzyme reaction than Atg +/+ mice. The mean total number of N-NOS-positive cells per 100 glomeruli was 6 times higher in Atg -/- mice than in Atg +/+ mice. Semiquantitative reverse transcription-PCR revealed an increase in the N-NOS mRNA level in renal cortical tissue of Atg -/- mice compared with Atg +/+ mice. Furthermore, the selective inhibition of N-NOS activity by 7-nitrondazole significantly decreased the level of renal renin mRNA in Atg -/- mice. These results suggest that increased N-NOS activity at the macula densa is involved a renal renin overproduction in Atg -/- mice.

Angiotensinogen↗

PubMed2001

A behavioral study of alpha-1b adrenergic receptor knockout mice: increased reaction to novelty and selectively reduced learning capacities.

Knockout mice lacking the alpha-1b adrenergic receptor were tested in behavioral experiments. Reaction to novelty was first assessed in a simple test in which the time taken by the knockout mice and their littermate controls to enter a second compartment was compared. Then the mice were tested in an open field to which unknown objects were subsequently added. Special novelty was introduced by moving one of the familiar objects to another location in the open field. Spatial behavior and memory were further studied in a homing board test, and in the water maze. The alpha-1b knockout mice showed an enhanced reactivity to new situations. They were faster to enter the new environment, covered longer paths in the open field, and spent more time exploring the new objects. They reacted like controls to modification inducing spatial novelty. In the homing board test, both the knockout mice and the control mice seemed to use a combination of distant visual and proximal olfactory cues, showing place preference only if the two types of cues were redundant. In the water maze the alpha-1b knockout mice were unable to learn the task, which was confirmed in a probe trial without platform. They were perfectly able, however, to escape in a visible platform procedure. These results confirm previous findings showing that the noradrenergic pathway is important for the modulation of behaviors such as reaction to novelty and exploration, and suggest that this is mediated, at least partly, through the alpha-1b adrenergic receptors. The lack of alpha-1b adrenergic receptors in spatial orientation does not seem important in cue-rich tasks but may interfere with orientation in situations providing distant cues only.

Animals↗

PubMed2005

Reduced appetite for caffeine in adenosine A(2A) receptor knockout mice.

Adenosine A(2A) receptor knockout mice (A(2A)R KO) were compared to wild-type controls (A(2A)R WT) in a caffeine intake paradigm. When mice had ad libitum access to caffeine (0.3 g/l) and water in a two-bottle paradigm for 12 consecutive days, adenosine A(2A)R KO mice drank less caffeinated solution, demonstrating a reduced appetite for caffeine as compared to adenosine A(2A)R WT mice. These data reveal an important role for the adenosine A(2A) receptor in the appetitive properties of caffeine.

Adenosine A2 Receptor Antagonists↗

PubMed2003

Abnormal myocardial contraction in alpha(1A)- and alpha(1B)-adrenoceptor double-knockout mice.

We used double-knockout mice (ABKO) lacking both predominant myocardial alpha(1)-adrenergic receptor (AR) subtypes (alpha(1A) and alpha(1B)) to determine if alpha(1)-ARs are required for normal myocardial contraction. Langendorff-perfused ABKO hearts had higher developed pressure than wild type (WT) hearts (123 +/- 3 mmHg n = 22 vs. 103 +/- 3 mmHg, n = 38, P < 0.001). Acutely inhibiting alpha(1)-ARs in WT hearts with prazosin did not increase pressure, suggesting that the increased pressure of ABKO hearts was mediated by long-term trophic effects on contraction rather than direct regulatory effects of alpha(1)-AR removal. Similar to perfused hearts, ABKO ventricular trabeculae had higher submaximal force at 2 mM extracellular [Ca(2+)] than WT (11.4 +/- 1.7 vs. 6.9 +/- 0.6 mN/mm(2), n = 8, P < 0.05); however, the peaks of fura-2 Ca(2+) transients were not different (0.79 +/- 0.11 vs. 0.75 +/- 0.16 microM, n = 10-12, P > 0.05), suggesting ABKO myocardium had increased myofilament Ca(2+)-sensitivity. This conclusion was supported by measuring the Ca(2+)-force relationship using tetanization. Increased myofilament Ca(2+)-sensitivity was not explained by intracellular pH, which did not differ between ABKO and WT (7.41 +/- 0.01 vs. 7.39 +/- 0.02, n = 4-6, P > 0.05; from BCECF fluorescence). However, ABKO displayed impaired troponin I phosphorylation, which may have played a role. In contrast to increased submaximal force, ABKO trabeculae had lower maximal force than WT at high extracellular [Ca(2+)] (29.6 +/- 1.9 vs. 37.6 +/- 1.4 mN/mm(2), n = 7, P < 0.01). However, peak cytosolic [Ca(2+)] was not different (1.13 +/- 0.15 vs. 1.19 +/- 0.04 microM, n = 6-7, P > 0.05), suggesting ABKO myocardium had impaired myofilament function. Finally, ABKO myocardium had decreased responsiveness to beta-AR stimulation. We conclude: alpha(1)-ARs are required for normal myocardial contraction; alpha(1)-ARs mediate long-term trophic effects on contraction; loss of alpha(1)-AR function causes some of the functional abnormalities that are also found in heart failure.

Animals↗

PubMed2001

Role of hypothalamic-pituitary axis in morphine-induced alteration in thymic cell distribution using mu-opioid receptor knockout mice.

Mu-opioid receptor knockout mice (MORKO), were used to address two questions: (1) if morphine induced decrease in thymic weight and cell distribution is mediated by the mu-opioid receptor and (2) the role of corticosteroids in morphine mediated alteration in thymic cell distribution. Our result show that morphine mediated increase in plasma corticosterone is mediated by the mu-opioid receptor since morphine at doses as high as 25 mg/kg-body weight does not increase plasma corticosterone levels in the MORKO. In addition, we have also shown that morphine treatment results in the differentiation of CD4+CD8+ (double positive cells) to single positive CD4+ cells while dexamethasone treatment results in the deletion of CD4+CD8+ (double positive) cells.

Adrenocorticotropic Hormone↗

PubMed2000

Insights derived from ACE knockout mice.

The evaluation of ACE knockout mice has illustrated the tremendous physiologic importance of the RAAS. We have discussed how interruption of this system influences blood pressure, renal function, renal development, serum and urine electrolyte composition, haematocrit and male reproductive capacity. This body of data underlines the modelling of the RAAS as a type of biological machine that is positioned to respond to environmental insult and to maintain a homeostasis of blood pressure, blood volume and electrolyte composition. These data also emphasise Harry Goldblatt's seminal observation that the kidney and the RAAS are intimately linked in the regulation of normal blood pressure.

Animals↗

PubMed2005

Sex differences in the regulation of serotonergic transmission and behavior in 5-HT receptor knockout mice.

Few studies have examined the relationship between genetics, stress, and sex-linked differences in neurotransmitter systems. Examining serotonin (5-HT) receptor knockout mice on stress-induced behavioral depression, female 5-HT1B receptor knockout mice demonstrated significantly reduced immobility than either male 5-HT1B receptor knockout mice or male and female wild-type mice on the tail suspension test (TST) and forced swimming test. The behavioral phenotype was identified as likely due to a disinhibition of 5-HT release, because depletion of 5-HT with parachlorophenylalanine selectively reduced immobility of female 5-HT1B receptor knockout mice in the TST. In contrast, male and female 5-HT1A receptor knockout mice demonstrated reduced immobility compared with control mice, but the depletion of 5-HT with PCPA did not reverse the antidepressant-like phenotype. Microdialysis studies confirmed significantly higher baseline levels of hippocampal 5-HT in female, but not male, 5-HT1B receptor knockout mice. Both male and female 5-HT1B receptor knockout mice demonstrated augmented dialysate responses to fluoxetine. Also, both male and female 5-HT1B receptor knockout mice demonstrated reductions of immobility in the TST after treatment with fluoxetine. Therefore, female 5-HT1B receptor knockout mice demonstrate a sex-linked disinhibition of 5-HT release that sustained higher baseline levels of hippocampal 5-HT and behavioral vulnerability to 5-HT depletion.

Animals↗

PubMed1997

Tamoxifen decreases cholesterol sevenfold and abolishes lipid lesion development in apolipoprotein E knockout mice.

BACKGROUND: Apolipoprotein E (apo E) knockout mice develop severe vascular lipid lesions resembling human atherosclerotic plaques, irrespective of the fat content of their diet. METHODS AND RESULTS: Oral tamoxifen (TMX) at a dose of 1.9 mg.kg body wt-1.d-1 abolished lipid lesion development, assayed by oil red O staining, whether the mice were fed a normal diet or a diet with high fat content. The TMX-treated mice showed a sevenfold decrease in total cholesterol. However, the proportion of plasma cholesterol present in VLDL remained unchanged, whereas the proportion in LDL decreased by 37%, and that in HDL increased by 64%. Consistent with the shift from LDL to HDL cholesterol, there was a 62% decrease in total triglycerides. The concentrations of active and acid-activatable latent plus active TGF-beta in the aorta were substantially elevated by TMX (87% and 24% increase, respectively). CONCLUSIONS: Although the mechanism of cardiovascular protection by TMX in apo E knockout mice is unknown, the inhibition of lipid lesion formation may be attributable to the changes in lipoprotein profile and the elevated levels of TGF-beta, both of which are thought to be protective against atherosclerosis in humans and animal models.

Animals↗

PubMed2005

Histochemical characteristics of soleus muscle in angiotensin-converting enzyme gene knockout mice.

We examined the histochemical characteristics of soleus muscle in the angiotensin-converting enzyme (ACE) gene (Ace in mice, ACE in humans) knockout mice. Serial sections of soleus muscle of wild-type (Ace+/+, n=20) and heterozygous mutant (Ace+/-, n=24) mice were stained for myosin adenosine triphosphatase activity to identify different muscle fiber types. Capillaries were visualized by amylase-periodic acid-Schiff staining. ACE activity in the serum and gastrocnemius muscle was higher in male mice than in female mice. Female and male Ace+/- mice had markedly lower ACE activity in the serum and the gastrocnemius muscle than did female and male Ace+/+ mice, respectively. In both male and female mice, the composition of fiber types (type I and IIa) did not differ significantly between Ace+/+ and Ace+/- mice. There was no significant gender difference in capillary density. Ace+/- mice had significantly more capillaries around type IIa fibers (5.44 +/- 0.18 vs. 5.01 +/- 0.13, p<0.05) than Ace+/+ mice. The differences in the number of capillaries around type I fibers and in the number of capillaries around per fiber (capillary:fiber ratio) between Ace+/- and Ace+/+ mice were not significant (p<0.1). There was no significant difference in the mean cross-sectional area occupied by one capillary and the number of capillaries per fiber area between Ace+/+ and Ace+/- mice. In conclusion, knockout of the Ace gene in mice increased capillary density, as expressed by the mean number of capillaries around type IIa fibers. This finding suggests a possible mechanism for the cardioprotective effects of ACE inhibitors.

Angiotensin-Converting Enzyme Inhibitors↗

PubMed2002

Susceptibility to Cryptosporidium parvum infections in cytokine- and chemokine-receptor knockout mice.

To determine the role of cytokines and a chemokine receptor in the susceptibility to, and outcome of, infection, 4 different knockout mice (IL-4, IL-10, IL-12, and CCR5) were infected with Cryptosporidium parvum and monitored for infection intensity by collection of fecal pellets from individual mice. Because adult immunocompetent mice are refractory to infection, wild-type mice on the same background as the knockout mice (C57BL/6) were used as a negative control. No infection was detected over a 4-wk time period in IL-4, IL-10, and CCR5 knockout mice inoculated with 106 oocysts. IL-12 knockout mice inoculated with as little as 100 oocysts shed up to 10,000 oocysts/100 microl of feces on the peak infection day (day 8) and were able to fully recover by 2 wk after infection. IL-12 is an important inducer of IFN-gamma, which probably accounted for susceptibility to infection. Previous studies using IFN-gamma knockout mice have shown strain-related differences in infection intensity and outcome, with increased parasite loads and decreased survival among IFN-gamma knockout mice on a C57BL/6 background compared with those on a BALB/c background. Similar results were observed in IL-12 knockout mice on a BALB/c background, which exhibited little or no infection, despite higher levels of inoculation (10(6) oocysts/mouse).

Animals↗

PubMed1999

Attenuation of renal ischemia-reperfusion injury in inducible nitric oxide synthase knockout mice.

Renal ischemia-reperfusion (I/R) injury was investigated in inducible nitric oxide synthase (iNOS) knockout mice. After a 26-min bilateral renal pedicle clamp, serum creatinine concentrations (in mg/dl) in wild-type mice after a 24-h reperfusion were 0.25 +/- 0.03 in sham-operated controls and 2.3 +/- 0.38 in ischemic mice (P < 0. 01); after 48 h, concentrations (in mg/dl) were 0.25 +/- 0.03 in controls and 2.0 +/- 0.18 in ischemic mice (P < 0.01). iNOS knockout mice demonstrated an attenuation of serum creatinine concentration after renal I/R injury. Serum creatinine concentrations (mg/dl) after a 24-h reperfusion were 2.3 +/- 0.22 in wild-type ischemic and 1.21 +/- 0.25 in iNOS knockout ischemic mice (P < 0.05); after 48 h, concentrations were 2.0 +/- 0.18 in wild-type ischemic and 0.96 +/- 0.25 in iNOS knockout ischemic mice (P < 0.01). Histological scoring of acute tubular necrosis in iNOS knockout mice was decreased compared with that in wild-type controls (0.88 +/- 0.2 vs. 3.3 +/- 0. 3, P < 0.05). iNOS protein in the renal cortex of wild-type mice subjected to renal I/R injury was undetectable up to 48 h. However, a strong upregulation of heat shock protein 72 expression was observed in renal cortex of iNOS knockout mice under basal conditions. In conclusion, kidneys of iNOS knockout mice were protected against ischemic acute renal failure. This protective effect may be related to a compensatory upregulation of heat shock protein 72.

Animals↗

PubMed2001

Erythrocyte water permeability and renal function in double knockout mice lacking aquaporin-1 and aquaporin-3.

Aquaporin (AQP) water channel AQP3 has been proposed to be the major glycerol and non-AQP1 water transporter in erythrocytes. AQP1 and AQP3 are also expressed in the kidney where their deletion in mice produces distinct forms of nephrogenic diabetes insipidus. Here AQP1/AQP3 double knockout mice were generated and analyzed to investigate the functional role of AQP3 in erythrocytes and kidneys. 53 double knockout mice were born out of 756 pups from breeding double heterozygous mice. The double knockout mice had reduced survival and impaired growth compared with the single knockout mice. Erythrocyte water permeability was 7-fold reduced by AQP1 deletion but not further reduced in AQP1/AQP3 null mice. AQP3 deletion did not affect erythrocyte glycerol permeability or its inhibition by phloretin. Daily urine output in AQP1/AQP3 double knockout mice (15 ml) was 9-fold greater than in wild-type mice, and urine osmolality (194 mosm) was 8.4-fold reduced. The mice remained polyuric after DDAVP administration or water deprivation. The renal medulla in most AQP1/AQP3 null mice by age 4 weeks was atrophic and fluid-filled due to the severe polyuria and hydronephrosis. Our data provide direct evidence that AQP3 is not functionally important in erythrocyte water or glycerol permeability. The renal function studies indicate independent roles of AQP1 and AQP3 in countercurrent exchange and collecting duct osmotic equilibration, respectively.

Animals↗

PubMed1996

Preservation of spatial learning in fyn tyrosine kinase knockout mice.

Previous work has shown that knockout mice lacking the fyn tyrosine kinase gene (fyn-/-) are impaired in spatial learning. Here, we have re-examined the spatial learning of fyn-/- mutants in an open field water maze. Unlike wild-type mice, fyn-/- knockouts often floated without moving when placed in the water but could swim adequately when their hind feet were mechanically stimulated. Under these conditions, fyn-/- mice showed significant improvement over trials in locating a hidden platform. On a transfer trial, at the end of training, they spent a disproportionate amount of time swimming in the location of the previously hidden platform. These findings suggest that fyn-/- knockouts are capable of spatial learning, but suffer an impairment that compromises their ability to swim normally.

Animals↗

PubMed2004

Altered emotional behaviors and the expression of 5-HT1A and M1 muscarinic receptors in micro-opioid receptor knockout mice.

Anxiety and depression alterations have been reported in micro-opioid receptor knockout mice after exon 2 disruption. However, emotional behaviors, such as novelty and emergence responses have not been reported in micro-opioid receptor knockout mice due to the disruptions of exon 2 and 3. Here, we report that mu-opioid receptor knockout mice, with deletion of exon 2 and 3, display significant emotional behavior changes; they showed less anxiety in the elevated plus maze and emergence tests, reduced response to novel stimuli in the novelty test, and less depressive-like behavior in the forced-swim test. Analysis of the compensatory mechanism in mu-opioid receptor knockout mice revealed that the M1 mRNA levels were reduced in the cortex, caudate putamen, nucleus accumbens, and hippocampus, and that M1 receptor levels were reduced in the nucleus accumbens, CA1, and the dentate gyrus of the hippocampus, versus the wild-type. However, 5-HT1A receptor levels were significantly elevated in the cerebral cortex and in the hypothalamus of mu-opioid receptor knockout mice versus the wild-type. These aberrant emotional behavioral phenotypes are possibly related to M1 and 5-HT1A receptor alterations in the micro-opioid receptor knockout mice. Overall, our study suggests that micro-opioid receptor may play a role in the modification of emotional responses to novelty, anxiety, and depression.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2004

The effects of aspirin on gastric mucosal integrity, surface hydrophobicity, and prostaglandin metabolism in cyclooxygenase knockout mice.

BACKGROUND & AIMS: Insight into the role of the different cyclooxygenase isoforms in prostaglandin biosynthesis, surface hydrophobicity, and gastric mucosal barrier integrity can be gained by comparing the effects of luminal damaging agents in wild-type and cyclooxygenase knockout mice. METHODS: Fasted wild-type, cyclooxygenase-1, and cyclooxygenase-2 knockout mice were intragastrically administered saline, 0.6N HCl, or aspirin (aspirin 20 mmol/L) in combination with 0.6N HCl and killed 1 hour later, at which time the gastric lesion score was assessed and biopsy samples were taken for surface, biochemical, and morphological analyses. RESULTS: The gastric mucosa of cyclooxygenase-1 knockout mice was more severely injured by both HCl alone and aspirin/HCl than that of wild-type and cyclooxygenase-2 knockout mice. HCl alone and aspirin/HCl also induced a more profound decrease in surface hydrophobicity in cyclooxygenase-1 knockout mice than in wild-type mice, whereas this surface property was unaffected in cyclooxygenase-2 knockout mice. The gastric injury induced by aspirin/HCl in cyclooxygenase-1 knockout mice could be prevented if the animals were treated with phosphatidylcholine-associated aspirin. Aspirin/HCl, in comparison to saline or HCl alone, induced a 4-6-fold increase in gastric mucosal prostaglandin E(2) concentration in the cyclooxygenase-1 knockout mice, whereas it decreased prostaglandin E(2) levels in wild-type and cyclooxygenase-2 knockout mice. This paradoxical aspirin-induced increase in gastric prostaglandin E(2) in cyclooxygenase-1 knockout mice seemed to correspond to an increase in cyclooxygenase-2 messenger RNA and protein expression. The gastric lesion score seemed to be significantly associated with alterations in surface hydrophobicity but not with mucosal prostaglandin E(2) concentration. CONCLUSIONS: Our evidence on cyclooxygenase knockout mice suggests that aspirin predominantly causes gastric injury by a non-prostaglandin mechanism, perhaps by attenuating surface hydrophobicity, a possibility supported by the low gastric toxicity of phosphatidylcholine/aspirin. However, prostaglandins generated by cyclooxygenase-1 may play an important permissive role in maintaining gastric mucosal barrier integrity. Aspirin seems to paradoxically increase the gastric mucosal prostaglandin E(2) concentration in cyclooxygenase-1 knockout mice, possibly by the induction of cyclooxygenase-2.

Animals↗

PubMed1997

Decreased HDL cholesterol levels but normal lipid absorption, growth, and feeding behavior in apolipoprotein A-IV knockout mice.

To determine the physiological role of apolipoprotein (apo) A-IV, knockout mice were created by gene targeting in embryonic stem cells. In apoA-IV knockout mice, plasma cholesterol and triglyceride levels were reduced 25% and 44%, respectively, compared with controls. These changes were accounted for by decreased high density (HDL) and very low density lipoprotein (VLDL) levels, respectively, and metabolic studies indicated increased HDL-cholesteryl ester (CE) fractional catabolic rate (FCR) and reduced VLDL transport rate (TR), respectively. ApoA-IV knockout mice had greater than 70% reductions in both hepatic and intestinal apoC-III RNA levels and a similar reduction in the plasma apoC-III level. Complementation analysis, via crossbreeding of a mouse apoC-III transgene onto both the normal and apoA-IV knockout backgrounds, clearly demonstrated that the low triglyceride (VLDL) level in the apoA-IV knockout mice was due to alterations in apoC-III and not apoA-IV. ApoA-IV knockout mice had normal growth, feeding behavior, and lipid absorption, except male mice showed increased food intake in the 2 h after an 18-h fast, suggesting that under some circumstances apoA-IV might serve as a satiety factor. In summary, studies in apoA-IV-induced mutant mice have demonstrated a role for apoA-IV in increasing HDL cholesterol by inhibiting HDL cholesteryl ester FCR yet argue against the apolipoprotein as an overall important mediator of lipid absorption/metabolism.

Animals↗