Additional Selected JAX® Mice Models for Metabolic Research

Some of the following strains are not necessarily models but may be used as “tools” in diabetes & obesity research

A/J

000646

• Whether fed chow, high-fat, or a high cholesterol-containing diet, this strain is resistant to diabetes and obesity (Surwit et al. 1995; Rossmeisl et al. 2003).
• One of the lowest glucose levels of all inbred mouse strains

ALR/LtJ and ALS/LtJ

003070 and 003072

• Useful for a variety of diabetes- and obesity-related research, including type 1 diabetes, type 2 diabetes, islet transplantation, adult-onset moderate obesity without diabetes, metabolism, and toxicology research
• Alloxan-untreated ALS/LtJ mice become obese and extremely hyperinsulinemic; males becoming progressively glucose intolerant; subset of these males develops spontaneous type 2 diabetes that responds to anti-oxidant therapy (Mathews et al. 2004)
• ALR/LtJ mice have normal glucose tolerance but gain weight rapidly (females weigh as much as males do by 50 weeks); may be used as controls for ALS/LtJ mice; genetically very similar to type 1 diabetes-prone NOD/ShiLtJ mice but are very resistant to autoimmune type 1 diabetes, partly because they have unusually strong systemic defenses against the generation of free radicals (Graser et al. 1999; Mathews et al. 2001, 2002).

B6.129S7-Ldlr^tm1Her/J

002207

• Males fed diabetogenic high-fat diets exhibit metabolic syndrome phenotypes: hypertriglyceridemia, hypercholesterolemia, hyperleptinemia, hyperinsulinemia, moderate hyperglycemia, obesity, high vascular calcification, atherosclerosis, and high free fatty acid levels (Merat et al. 1999; Schreyer et al. 2002; Towler et al. 1998)
• May also be used as a diet-induced obesity (DIO) model

B6.Cg- A^y/J

000021

• Heterozygotes become obese, but, unlike KK.Cg-A^y/J heterozygotes, only mildly diabetic (Reddi and Camerini-Davalos 1988; Taylor et al. 1999).

B6(Cg)-Tub^tub/J

000562

• Homozygotes develop maturity-onset obesity, recognizable at three to four months in males and at four to six months in females
• Although plasma insulin rises before obvious signs of obesity and may be 20 times higher than normal in six-month olds, tubby mice do not become diabetic
• High HDL levels, resistant to diet-induced atherosclerosis
• Retinal degeneration and progressive hearing loss (Nishina et al. 1994; Noben-Trauth et al. 1996)
• Both sexes fertile

B6.HRS(BKS)-Cpe^fat/J

003923

• Diabetes in homozygotes characterized by hyperglycemia and insulin resistance
• Becomes obese earlier and appears healthier (no hydronephrosis, fewer malocclusions) than BKS.HRS-Cpe^fat/J
• Females become heavier than males
• Both sexes become obese later than B6.Cg-Lep^ob/J (000632) and BKS.Cg-Dock7^m +/+ Lepr^db/J (000642) (Walker and Truett 1997).
• Two modifier loci (Mobe1, Mobe2, formerly called Moo1 and Moo2) regulate total fat mass: BTBR alleles of these loci semi-dominantly increase body mass (Clee et al. 2005)

Ins2^Akita mutants

Ins2^Akita mutants are suitable for a wide variety of diabetes- and obesity-related research, including hyperglycemia, hypoinsulinemia, impaired insulin processing, insulin receptors and growth factors, islet transplantation, mature onset of type 1 diabetes in young mice, and pancreas defects.

C57BL/6-Ins2^Akita/J

003548

• Models non-obese, early onset type 2 diabetes of autosomal dominant inheritance
• Untreated homozygotes rarely live past 12 weeks; heterozygotes viable and fertile
• Diabetes characterized by hyperglycemia, hypoinsulinemia, polydipsia, and polyuria by three to four weeks
• Insulitis-free symptoms more severe and progressive in males
• Mean lifespan of diabetic males is 305 days, significantly shorter than that of nondiabetics (690 days)
• Mortality rates of diabetic and nondiabetic females comparable
• Heterozygotes have few islets with relatively few beta cells (release very little mature insulin) but respond to exogenously administered insulin, indicating that Ins2^Akita mice are an excellent substitute for mice made insulin-dependent-diabetic with alloxan or streptozotocin
• Heterozygotes do not need to be treated with a diabetogen to induce hyperglycemia, hence ideally suited to syngenic islet transplantation (Mathews et al. 2002)
• Because heterozygotes survive a long time with chronic hyperglycemia without insulin therapy, they are used to study the development of diabetic complications, most notably diabetic neuropathy and nephropathy (Breyer and Tchekneva 2006; Choeiri et al. 2005)
• Older mutants have difficulty walking and have slow reaction times, normal learning ability and memory
• Progressive retinal abnormalities begin at about 12 weeks (after hyperglycemia develops)

B6.Cg-Rag1^tm1Mom Ins2^Akita/J 

004369

• Spontaneously develops diabetes when young (beta cell deficiency)
• Severely immunocompromised (no B and T cells)
• Ideally suited for allogeneic and xenogeneic islet, islet cell, and stem cell transplantation research

LG/J and SM/J 

000675 and 000687

• Often crossed with each other or to A/J (000646) or NZB/BINJ (000684) to find obesity, diabetes, and cardiovascular disease QTLs (Clee and Attie 2006)
• Differ in many traits, including obesity, plasma glucose, glucose tolerance, and response to high-fat feeding (Ehrich et al. 2003)
• When both are fed a high-fat diet, SM mice have higher serum glucose levels (Ehrich et al. 2003)
• Several QTLs for insulin, glucose, and glucose tolerance identified in the LGXSM RI strains (loci affecting glucose and insulin resistance likely different) (Cheverud et al. 2004a, 2004b)
• Several SMXA RI strains have different body weights and plasma insulin levels (Anunciado et al. 2000)
• SMXA-5, develops insulin resistance, increased β-cell mass, and may be a useful diabetes model (Kobayashi et al. 2004, 2006; Anunciado et al. 2000)
• Analysis of an F2 intercross between SMXA-5 and SM revealed several loci affecting plasma glucose levels, insulin levels, and glucose tolerance. One of these loci, on Chr 2, harbors two A/J-derived alleles that contribute to impaired glucose tolerance (Kobayashi et al. 2004)

NON/ShiLtJ

002423

• Diet induced obesity when fed a 45 kcal% fat diet
• Impaired glucose tolerance, and moderate transient hyperglycemia
• Late developing hyperinsulinemia (20-24 weeks of age)
• Elevated plasma triglycerides, free fatty acids, leptin and resistin
• Aging-dependent, mild glomerular nephropathy (Leiter et al. 1998)

NOD/ShiLtJ-Lepr^db-5J/LtJ

004939

• Homozygotes of both sexes develop juvenile onset obesity and type 2 diabetes
• Hyperphagic by five weeks, both sexes hyperglycemic within one to two weeks of weaning
• Do not require insulin therapy for long tem survival (39+ weeks)
• Chronically elevated insulin and leptin levels maintained over periods up to 1 year
• Islet hypertrophy with beta cell hyperplasia typically not restricted by insulitis, which, when present, is primarily peri-vascular/periductular and not intra-islet
• About 1/3 of progress to end-stage type 2 diabetes (low body weight and plasma insulin; about 2/3 stay obese (35-45g) and exhibit beta cell hypertrophy/hyperplasia (Lee et al. 2005)
• Serum lipid levels normal
• No significant liver or kidney pathology (Lee et al. 2005)
• Whereas splenic leukocytes from young, hyperglycemic mutants transferred into NOD.Rag1 recipients do not transfer type I diabetes over 13 weeks, wild-type donor cells do; however, widespread insulitis is transferred by Lepr^db-5J donors, indicating that their splenocytes contain a less-activated effector population at the time of transfer
• Reciprocal bone marrow transfers confirm that Lepr^db-5J marrow contains diabetogenic stem cells; however, the slower diabetes generated by either wild-type or mutant marrow transferred into irradiated Lepr^db-5J recipients indicates that the disturbed metabolic milieu produced by the obesity mutation is the major reason for suppressing the diabetogenic potential of marrow precursors (Lee et al. 2006)
• May be used to research the interaction between the endocrine and immune system in type 1 diabetes-prone mice, understanding the trophic factors generated to produce robust proliferation of B-cells, and studying the involvement of leptin signaling in cueing the cytopathic function of autoimmune T-effector cells

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