Correlated changes in fertility and fitness traits in lines of oMt1a-oGH transgenic mice selected for increased 8-week body weight *

2000 ◽  
Vol 117 (2) ◽  
pp. 83-95 ◽  
Author(s):  
F. Siewerdt ◽  
E. J. Eisen ◽  
J. D. Murray
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Fitness Traits

Reduction of dietary obesity in aP2-Ucp transgenic mice: physiology and adipose tissue distribution

1996 ◽  
Vol 270 (5) ◽  
pp. E768-E775 ◽  
Author(s):  
J. Kopecky ◽  
Z. Hodny ◽  
M. Rossmeisl ◽  
I. Syrovy ◽  
L. P. Kozak
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Transgenic Mice ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Gene Promoter ◽  
Lipid Binding ◽  
Brown Fat ◽  
Mitochondrial Uncoupling ◽  
Dietary Obesity

We seek to determine whether increased energy dissipation in adipose tissue can prevent obesity. Transgenic mice with C57BL6/J background and the adipocyte lipid-binding protein (aP2) gene promoter directing expression of the mitochondrial uncoupling protein (UCP) gene in white and brown fat were used. Physiologically, UCP is essential for nonshivering thermogenesis in brown fat. Mice were assigned to a chow or a high-fat (HF) diet at 3 mo of age. Over the next 25 wk, gains of body weight were similar in corresponding subgroups (n = 6-8) of female and male mice: 4-5 g in chow nontransgenic and transgenic, 20 g in HF nontransgenic, and 9-11 g in HF transgenic mice. The lower body weight gain in the HF transgenic vs. nontransgenic mice corresponded to a twofold lower feed efficiency. Gonadal fat was enlarged, but subcutaneous white fat was decreased in the transgenic vs. nontransgenic mice in both dietary conditions. The results suggest that UCP synthesized from the aP2 gene promoter is capable of reducing dietary obesity.

Consequences of thyroid hormone deficiency induced by the specific ablation of thyroid follicle cells in adult transgenic mice

1994 ◽  
Vol 143 (1) ◽  
pp. 107-120 ◽  
Author(s):  
H Wallace ◽  
K McLaren ◽  
R Al-Shawi ◽  
J O Bishop
Keyword(s):  
Body Weight ◽  
Thyroid Hormone ◽  
Transgenic Mice ◽  
Follicle Cells ◽  
Hormone Deficiency ◽  
Mrna Levels ◽  
Thyroid Follicle ◽  
Receptor Mrna ◽  
The Many ◽  
Tsh Levels

Abstract The herpes simplex type 1 virus thymidine kinase (HSV1-TK) reporter gene was coupled to a bovine thyroglobulin promoter (TG-tk construct). Within the thyroid glands of transgenic mice expression was confined to thyroid follicle cells. Infusion of Ganciclovir (9-[(1,3-dihydroxy-2-propoxy)methyl]guanine) to 8 to 12 week transgenic females led to the complete loss of thyroid HSV1-TK activity (at 3 to 4 days) and thyroid follicles (between 7 and 14 days). During the first 5 days of treatment a single reciprocal oscillation in circulating thyroxine (T4) and TSH levels occurred. By 14 days the circulating triiodothyronine (T3) and T4 levels of all treated animals were below the detection limits of the assays, while TSH levels were elevated ten-fold and continued to increase thereafter. During 14 days of treatment the thyroids regressed, protein content fell by 80–90% and the C cells, normally dispersed within the central region of each gland, came together in aggregates. Pituitary GH levels in females rose and fell back to normal within 14 days and between 14 and 28 days fell to a level comparable with that of GH-deficient lit/lit mice. The levels of hepatic GH receptor mRNA and the predominant 6·6 kb T3 receptor mRNA were unaffected by thyrocyte ablation. Thyrocyte ablation had no effect on the level of prolactin (Prl) receptor mRNA in females, but increased Prl receptor mRNA levels in males and eliminated group 1 major urinary protein (MUP) mRNA in females. T4 replacement reversed the effects of thyrocyte ablation on MUP mRNA in females and on Prl receptor mRNA in males. Despite the many physiological changes induced by thyrocyte ablation, ablated mice have been maintained for up to 1 year without thyroid hormone supplementation. T4-deficient females were normally fertile and carried pups to term. Although transgenic males expressed HSV1-TK ectopically in spermatids and spermatozoa at levels similar to thyrocyte levels, a rate of Ganciclovir infusion which successfully ablated the thyrocytes did not affect the testis. As an alternative to infusion by minipump, thyrocyte ablation could be achieved by 6 twice-daily injections of Ganciclovir, at a level of 112 μg Ganciclovir/g body weight per day, and fetuses in utero could be thyrocyte ablated by administering 50 or 15 μg/g body weight per day to pregnant females between days 14 and 18 of gestation. These data demonstrate the potential value of transgenic thyrocyte ablation in the study of the effects of thyroid hormone deprivation. Journal of Endocrinology (1994) 143, 107–120

scholarly journals Loss of perlecan heparan sulfate glycosaminoglycans lowers body weight and decreases islet amyloid deposition in human islet amyloid polypeptide transgenic mice

2019 ◽  
Vol 32 (2) ◽  
pp. 95-102
Author(s):  
Andrew T Templin ◽  
Mahnaz Mellati ◽  
Raija Soininen ◽  
Meghan F Hogan ◽  
Nathalie Esser ◽  
...  
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Heparan Sulfate ◽  
Islet Amyloid Polypeptide ◽  
Amyloid Deposition ◽  
Secretory Product ◽  
Cell Area ◽  
Β Cell ◽  
Islet Amyloid

Abstract Islet amyloid is a pathologic feature of type 2 diabetes (T2D) that is associated with β-cell loss and dysfunction. These amyloid deposits form via aggregation of the β-cell secretory product islet amyloid polypeptide (IAPP) and contain other molecules including the heparan sulfate proteoglycan perlecan. Perlecan has been shown to bind amyloidogenic human IAPP (hIAPP) via its heparan sulfate glycosaminoglycan (HS GAG) chains and to enhance hIAPP aggregation in vitro. We postulated that reducing the HS GAG content of perlecan would also decrease islet amyloid deposition in vivo. hIAPP transgenic mice were crossed with Hspg2Δ3/Δ3 mice harboring a perlecan mutation that prevents HS GAG attachment (hIAPP;Hspg2Δ3/Δ3), and male offspring from this cross were fed a high fat diet for 12 months to induce islet amyloid deposition. At the end of the study body weight, islet amyloid area, β-cell area, glucose tolerance and insulin secretion were analyzed. hIAPP;Hspg2Δ3/Δ3 mice exhibited significantly less islet amyloid deposition and greater β-cell area compared to hIAPP mice expressing wild type perlecan. hIAPP;Hspg2Δ3/Δ3 mice also gained significantly less weight than other genotypes. When adjusted for differences in body weight using multiple linear regression modeling, we found no differences in islet amyloid deposition or β-cell area between hIAPP transgenic and hIAPP;Hspg2Δ3/Δ3 mice. We conclude that loss of perlecan exon 3 reduces islet amyloid deposition in vivo through indirect effects on body weight and possibly also through direct effects on hIAPP aggregation. Both of these mechanisms may promote maintenance of glucose homeostasis in the setting of T2D.

scholarly journals Correlated responses to selection for large body size in oMt1a-oGH transgenic mice: reproductive traits

2000 ◽  
Vol 75 (2) ◽  
pp. 199-208 ◽  
Author(s):  
K. R. PARKS ◽  
E. J. EISEN ◽  
I. J. PARKER ◽  
L. G. HESTER ◽  
J. D. MURRAY
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Reproductive Performance ◽  
Large Body ◽  
Low Frequency ◽  
High Growth ◽  
Reproductive Traits ◽  
Correlated Responses ◽  
Term Selection ◽  
Transgenic Lines

Correlated responses in female reproductive performance were evaluated following short-term selection within full-sib families for increased 8-week body weight in two replicates of four lines of mice: two ovine metallothionein–ovine growth hormone (oMt1a-oGH) transgene-carrier lines, one from a high-growth background (TM) and one from a control background (TC), and two non-transgenic lines, one from each of these genetic backgrounds (NM and NC, respectively). A fifth line (CC), not containing the transgene, served as a randomly selected control. The initial frequency of the oMt1a-oGH transgene construct in the TM and TC lines was 0·5. The frequency of transgenic females sampled at generations 7 and 8 of selection was 84·0% and 6·1% in the TC and TM lines, respectively. No significant female infertility differences were detected between transgene-carrier and non-transgenic lines or between transgenic and non-transgenic mice within carrier lines, whereas high-growth background lines had a higher infertility than control background lines (P < 0·05). Correlated responses in the TC transgene-carrier line were suggestive of reduced reproductive performance as indicated by increased post-implantation mortality (P < 0·05), number of dead fetuses plus implants (P < 0·05), and loss of fetuses from day 16 to parturition (P < 0·001). For the first two traits, the negative correlated responses were accounted for by the reduced performance of transgenic compared with non-transgenic females. Embryos carrying the transgene may also have a lower viability. In contrast, the NC non-transgenic line did not exhibit reduced reproductive performance for these traits. The low frequency of the transgene in the high-growth background TM line was associated with reduced fitness and a lower additive effect for 8-week body weight compared with the control background TC line.

Expression of human hepatic glucokinase in transgenic mice liver results in decreased glucose levels and reduced body weight

Diabetes ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 11-16 ◽  
Author(s):  
N. Hariharan ◽  
D. Farrelly ◽  
D. Hagan ◽  
D. Hillyer ◽  
C. Arbeeny ◽  
...  
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Glucose Levels ◽  
Reduced Body ◽  
Mice Liver

Expression of Human Hepatic Glucokinase in Transgenic Mice Liver Results in Decreased Glucose Levels and Reduced Body Weight

Diabetes ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 11-16 ◽  
Author(s):  
N. Hariharan ◽  
D. Farrelly ◽  
D. Hagan ◽  
D. Hillyer ◽  
C. Arbeeny ◽  
...  
Keyword(s):  
Body Weight ◽  
Transgenic Mice ◽  
Glucose Levels ◽  
Reduced Body ◽  
Mice Liver

Effects of growth hormone overproduction on grip strength of transgenic mice

1995 ◽  
Vol 133 (6) ◽  
pp. 735-740 ◽  
Author(s):  
Eckhard Wolf ◽  
Rüdiger Wanke ◽  
Emanuel Schenck ◽  
Walter Hermanns ◽  
Gottfried Brem
Keyword(s):  
Growth Hormone ◽  
Body Weight ◽  
Muscle Strength ◽  
Transgenic Mice ◽  
Least Squares ◽  
Grip Strength ◽  
Long Term Effects ◽  
Muscle Weight ◽  
Significant Difference

Wolf E, Wanke R, Schenck E, Hermanns W, Brem G. Effects of growth hormone overproduction on grip strength of transgenic mice. Eur J Endocrinol 1995;133:735–40. ISSN 0804–4643 Growth hormone (GH) is used by athletes like bodybuilders to increase muscle strength and weight gain. On the other hand, chronic hypersecretion of GH in active acromegaly may result in outwardly hypertrophied but functionally weaker muscles. As a model for studying long-term effects of GH on muscle strength, we analysed transgenic mice (TM) carrying rat phosphoenolpyruvate carboxykinasebovine GH (PEPCKbGH) fusion genes, which are expressed in liver and kidney but not in skeletal muscle. Circulating GH levels in TM ranged between 0.5 and 3 μg/ml, resulting in increased (p <0.001) body weight (wt) as well as increased (p <0.01) weights of forelimb and hindlimb muscles. However, muscle weight/body wt ratios of TM were 16–20% smaller than in controls (p<0.05), Forelimb grip strength of hemizygous TM (16 males, 132 ± 45 days old, body wt = 56.8 ± 8.3 g; 32 females, 146 ± 38 days old, body wt = 54.9 ± 6.1 g) and non-transgenic controls (28 males, 127 ± days old, body wt = 40.5±2.9 g; 33 females, 126 ±47 days old, body wt = 32.1 ± 3.6 g) was determined using an automated grip strength meter. Data were computed by analysis of variance, taking into account effects of group, sex and age. Least-squares means estimated for the grip strength (N) of male TM (1.91) and controls (1.92) were significantly (p<0.05) greater than those of female TM (1.78) and controls (1.61). A significant difference between groups was only seen in females (p <0.01). Least-squares means estimated for grip strength/body wt ratios (N/10 g) of male (0.34) and female TM (0.33) were 29% and 35% lower than those of male (0.48) and female controls (0.51), respectively (p <0.001). In summary, long-term elevated GH levels in TM increased muscle weight less efficiently than body weight, and muscle strength did not increase proportionally with muscle weight. Eckhard Wolf, Lehrstuhl für Molekulare Tierzucht und Haustiergenetik, Ludwig-Maximilians-Universität München, Würmtalstraβe 221, 81375 München, Germany

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