Difference in obesity phenotype between orexin-knockout mice and orexin neuron-deficient mice with same genetic background and environmental conditions

The present study was undertaken to determine whether the severity of renal failure or hypertension in homozygous cyclooxygenase (COX)-2-deficient (COX-2−/−) mice affected by genetic background or gender. COX-2 deletion was introduced into three congenic genetic backgrounds, 129/Sv (129/COX-2−/−), C57/BL6 (C57/COX-2−/−), and BALB/c (BALB/COX-2−/−), by backcrossing the original mixed-background knockout mice with the respective inbred strains for 9 or 10 generations. Evaluation of the severity of hypertension and renal failure was performed in knockout and wild-type mice at the age of 2.5–3.5 mo. Blood pressure measured by tail-cuff plethysmography was significantly elevated in the male 129/COX-2−/− mice (165.8 ± 9.2 vs. 116 ± 5.1 mmHg, P < 0.05), and to a much lesser extent in the female 129/COX-2−/− mice (127.4 ± 3.3 vs. 102.4 ± 3.3), whereas it was unchanged in the C57- or BALB/COX-2−/− mice regardless of gender. Urinary excretion of albumin, determined by EIA, was remarkably increased in the 129/COX-2−/− (16.4 ± 4.1 vs. 0.16 ± 0.043 mg albumin/mg creatinine, P < 0.001), and to a lesser extent in the male C57/COX-2−/− mice (0.595 ± 0.416 vs. 0.068 ± 0.019). Albumin excretion was not elevated in the male BALB/COX-2−/− or in female COX-2−/− mice on any of the three genetic backgrounds. Histological analysis showed abundant protein casts, dilated tubules, and infiltration of inflammatory cells in the male 129/COX-2−/− mice, but not in COX-2−/− mice in other strains or gender. However, the presence of small glomeruli in the nephrogenic zone was observed in all strains of COX-2 knockout mice, regardless of genetic background and gender. Therefore, we conclude that the severity of hypertension and renal failure in COX-2-deficient mice is influenced by genetic background and gender, whereas the incomplete maturation of outer cortical nephrons appears to be independent of genetic background effects.

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Genetic background-dependent abnormalities of the enteric nervous system and intestinal function in Kif26a-deficient mice

Scientific Reports ◽

10.1038/s41598-021-82785-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Yukiko Ohara ◽

Lisa Fujimura ◽

Akemi Sakamoto ◽

Youichi Teratake ◽

Shuichi Hiraoka ◽

...

Keyword(s):

Genetic Background ◽

Survival Rates ◽

Gastrointestinal Diseases ◽

Negative Regulator ◽

Enteric Neurons ◽

Enteric Neuron ◽

Protein Coding ◽

Underlying Mechanisms ◽

Functional Gastrointestinal Diseases ◽

Deficient Mice

AbstractThe Kif26a protein-coding gene has been identified as a negative regulator of the GDNF-Ret signaling pathway in enteric neurons. The aim of this study was to investigate the influence of genetic background on the phenotype of Kif26a-deficient (KO, −/−) mice. KO mice with both C57BL/6 and BALB/c genetic backgrounds were established. Survival rates and megacolon development were compared between these two strains of KO mice. Functional bowel assessments and enteric neuron histopathology were performed in the deficient mice. KO mice with the BALB/c genetic background survived more than 400 days without evidence of megacolon, while all C57BL/6 KO mice developed megacolon and died within 30 days. Local enteric neuron hyperplasia in the colon and functional bowel abnormalities were observed in BALB/c KO mice. These results indicated that megacolon and enteric neuron hyperplasia in KO mice are influenced by the genetic background. BALB/c KO mice may represent a viable model for functional gastrointestinal diseases such as chronic constipation, facilitating studies on the underlying mechanisms and providing a foundation for the development of treatments.

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Influence of Sex and Genetic Background on Anxiety-Related and Stress-Induced Behaviour of Prodynorphin-Deficient Mice

PLoS ONE ◽

10.1371/journal.pone.0034251 ◽

2012 ◽

Vol 7 (3) ◽

pp. e34251 ◽

Cited By ~ 22

Author(s):

Iris Kastenberger ◽

Christian Lutsch ◽

Herbert Herzog ◽

Christoph Schwarzer

Keyword(s):

Genetic Background ◽

Deficient Mice

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Effects of Genetic Background and Environmental Conditions on Amylopectin Chain-Length Distribution in a Recombinant Inbred Line of an Inter-subspecies Rice Cross

Journal of Agricultural and Food Chemistry ◽

10.1021/acs.jafc.0c02713 ◽

2020 ◽

Vol 68 (28) ◽

pp. 7444-7452

Author(s):

Ximing Xu ◽

Xiukun Li ◽

Zhibin Li ◽

Yang Li ◽

Kai Chen ◽

...

Keyword(s):

Chain Length ◽

Inbred Line ◽

Recombinant Inbred Line ◽

Environmental Conditions ◽

Recombinant Inbred ◽

Genetic Background ◽

Length Distribution ◽

Chain Length Distribution

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Effects of Genetic Background and Environmental Conditions on Texture Properties in a Recombinant Inbred Population of an Inter-Subspecies Cross

Rice ◽

10.1186/s12284-019-0286-x ◽

2019 ◽

Vol 12 (1) ◽

Cited By ~ 2

Author(s):

Ximing Xu ◽

Zhengjin Xu ◽

Yuji Matsue ◽

Quan Xu

Keyword(s):

Environmental Conditions ◽

Recombinant Inbred ◽

Genetic Background ◽

Texture Properties ◽

Inbred Population ◽

Recombinant Inbred Population

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Dual Ablation of Grb10 and Grb14 in Mice Reveals Their Combined Role in Regulation of Insulin Signaling and Glucose Homeostasis

Endocrine Reviews ◽

10.1210/edrv.30.5.9991 ◽

2009 ◽

Vol 30 (5) ◽

pp. 540-540

Author(s):

Lowenna J. Holt ◽

Ruth J. Lyons ◽

Ashleigh S. Ryan ◽

Susan M. Beale ◽

Andrew Ward ◽

...

Keyword(s):

Body Composition ◽

Glucose Homeostasis ◽

Insulin Signaling ◽

Knockout Mice ◽

Gene Knockout ◽

Physiological Role ◽

Whole Body ◽

Regulatory Function ◽

Double Knockout ◽

Deficient Mice

ABSTRACT Growth factor receptor bound (Grb)10 and Grb14 are closely related adaptor proteins that bind directly to the insulin receptor (IR) and regulate insulin-induced IR tyrosine phosphorylation and signaling to IRS-1 and Akt. Grb10- and Grb14-deficient mice both exhibit improved whole-body glucose homeostasis as a consequence of enhanced insulin signaling and, in the case of the former, altered body composition. However, the combined physiological role of these adaptors has remained undefined. In this study we utilize compound gene knockout mice to demonstrate that although deficiency in one adaptor can enhance insulin-induced IRS-1 phosphorylation and Akt activation, insulin signaling is not increased further upon dual ablation of Grb10 and Grb14. Context-dependent limiting mechanisms appear to include IR hypophosphorylation and decreased IRS-1 expression. In addition, the compound knockouts exhibit an increase in lean mass comparable to Grb10-deficient mice, indicating that this reflects a regulatory function specific to Grb10. However, despite the absence of additive effects on insulin signaling and body composition, the double-knockout mice are protected from the impaired glucose tolerance that results from high-fat feeding, whereas protection is not observed with animals deficient for individual adaptors. These results indicate that, in addition to their described effects on IRS-1/Akt, Grb10 and Grb14 may regulate whole-body glucose homeostasis by additional mechanisms and highlight these adaptors as potential therapeutic targets for amelioration of the insulin resistance associated with type 2 diabetes.

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Microarray analysis of hepatic genes differentially expressed in the presence of the unsaponifiable fraction of olive oil in apolipoprotein E-deficient mice

British Journal Of Nutrition ◽

10.1017/s0007114507657912 ◽

2007 ◽

Vol 97 (4) ◽

pp. 628-638 ◽

Cited By ~ 26

Author(s):

Sergio Acín ◽

María A. Navarro ◽

Javier S. Perona ◽

Joaquín C. Surra ◽

Natalia Guillen ◽

...

Keyword(s):

Gene Expression ◽

Olive Oil ◽

Genetic Background ◽

Dna Microarrays ◽

Biological Effects ◽

Hepatic Gene Expression ◽

Potential Candidate ◽

Unsaponifiable Fraction ◽

Olive Cultivar ◽

Deficient Mice

The hypothesis that the unsaponifiable fraction of olive oil dramatically influences hepatic gene expression was tested in mice. Two olive oils, obtained from the same olive cultivar but by different technological procedures, were characterized to show that they differed mainly in terms of the composition/quantity of this unsaponifiable fraction. Using DNA microarrays, hepatic gene expression was analysed in apoE-deficient mice fed one of two isoenergetic, isonitrogenous diets containing either 10 % (w/w) olive oil or unsaponifiable fraction-enriched olive oil. To provide an initial screening of potential candidate genes involved in a differential response, only genes with remarkably modified expression (signal log2 ratio >3 or < − 3) were further considered. The eleven genes fulfilling these prerequisites were confirmed by quantitative RT–PCR, and then analysed in apoE-deficient mice with a C57BL/6J genetic background. Orosomucoid and serum amyloid A2 were upregulated (to variable extents depending on the genetic background) in the absence of hepatic steatosis and inflammation. Fabp5 and Mt2 were also strongly upregulated. Several proteases were highly suppressed by the unsaponifiable-enriched olive diet, independent of the genetic background. The findings indicate that change in the expression of these genes is a good marker of the intake of the unsaponifiable fraction of olive oil. The results highlight the important biological effects of the unsaponifiable fraction of olive oil. The term ‘monounsaturated fatty acid-enriched oil’ no longer appears appropriate for describing all the oils to which it is currently applied since it does not adequately reflect that they have different biological effects.

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Carcinoma mucins trigger reciprocal activation of platelets and neutrophils in a murine model of Trousseau syndrome

Blood ◽

10.1182/blood-2011-07-368514 ◽

2011 ◽

Vol 118 (15) ◽

pp. 4015-4023 ◽

Cited By ~ 77

Author(s):

Bojing Shao ◽

Mark G. Wahrenbrock ◽

Longbiao Yao ◽

Tovo David ◽

Shaun R. Coughlin ◽

...

Keyword(s):

Murine Model ◽

Knockout Mice ◽

Fluid Phase ◽

Cell Types ◽

Src Family Kinases ◽

Cathepsin G ◽

Trousseau Syndrome ◽

Bidirectional Signaling ◽

Blocking Antibodies ◽

Deficient Mice

Abstract Trousseau syndrome is classically defined as migratory, heparin-sensitive but warfarin-resistant microthrombi in patients with occult, mucinous adenocarcinomas. Injecting carcinoma mucins into mice generates platelet-rich microthrombi dependent on P- and L-selectin but not thrombin. Heparin prevents mucin binding to P- and L-selectin and mucin-induced microthrombi. This model of Trousseau syndrome explains resistance to warfarin, which inhibits fluid-phase coagulation but not selectins. Here we found that carcinoma mucins do not generate microthrombi in mice lacking P-selectin glycoprotein ligand-1 (PSGL-1), the leukocyte ligand for P- and L-selectin. Furthermore, mucins did not activate platelets in blood from PSGL-1–deficient mice. Mucins induced microthrombi in radiation chimeras lacking endothelial P-selectin but not in chimeras lacking platelet P-selectin. Mucins caused leukocytes to release cathepsin G, but only if platelets were present. Mucins failed to generate microthrombi in cathepsin G-deficient mice. Mucins did not activate platelets in blood from mice lacking cathepsin G or protease-activated receptor-4 (PAR4), indicating that cathepsin G activates platelets through PAR4. Using knockout mice and blocking antibodies, we found that mucin-triggered cathepsin G release requires L-selectin and PSGL-1 on neutrophils, P-selectin on platelets, and Src family kinases in both cell types. Thus, carcinoma mucins promote thrombosis through adhesion-dependent, bidirectional signaling in neutrophils and platelets.

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Nanomechanics of Knockout Mouse Bones

MRS Proceedings ◽

10.1557/proc-975-0975-dd09-10 ◽

2006 ◽

Vol 975 ◽

Author(s):

N Beril Kavukcuoglu ◽

Adrian B. Mann

Keyword(s):

Mechanical Properties ◽

Knockout Mice ◽

Bone Mineralization ◽

Bone Matrix ◽

Wild Type ◽

Knock Out ◽

Bone Matrix Proteins ◽

Fibrillin 1 ◽

Deficient Mice ◽

Radial Axis

ABSTRACTOsteocalcin (OC) and osteopontin (OPN) are among the most abundant non-collagenous bone matrix proteins. Both have drawn interest from investigators studying their function in osteoporosis and it is known that mutations of these proteins can also have dramatic effects on the properties of bone. Other proteins including fibrillin 1 and 2 (FBN2) have been less widely studied, but can be mutated in some individuals resulting in connective tissue disorders. It has been reported that abnormal fibrillin may play a role in decreased bone mass. In this study bones from osteopontin (OPN), osteocalcin (OC) and fibrillin-2 (FBN2) knockout mice have been investigated. The study has identified how these proteins affect the bone's nanomechanical properties (hardness and elastic modulus). Nanoindentation tests were performed on the radial axis of cortical femora bones from the knockout mice and their wildtype controls. The results showed that young (age< 12 weeks) OPN knock-out bones have significantly lower mechanical properties than wild-type bones indicate a crucial role for OPN in early bone mineralization. After 12 weeks of age, the OPN knockout and wild-type control bones did not show any statistical difference. In OC deficient mice the mechanical properties were found to increase in the cortical mid-shaft of femora from 1 year old mice, suggesting an increase in bone mineralization, but 3 month old FBN2 deficient mice bones showed a decrease in mechanical properties across the cortical radial axis of the mid- femora.

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