Investigation on Biological Characteristics and Aging Phenotype of SHJH hr Mice

doi:10.12300/j.issn.1674-5817.2022.069

Abstract

Abstract:

Objective To measure and analyze biological characteristics and aging phenotype of SHJH ^hr mice and provide basic data for the application of the mouse model in aging mechanisms research and antiaging drug development. Methods With ICR mice of the same age as control group, the body mass growth data of SHJH ^hr mice at the age of 3 to 16 weeks, the reproduction ability of 1 to 4 fetuses and the life cycle of SHJH ^hr mice were measured. Blood routine (30 items) and serum biochemical indexes (25 items) of 6-week-old SHJH ^hr mice were measured. The venous blood of 8-week-old SHJH ^hr mice was collected for flow cytometry analysis to determine the content of immune cells. The aging bone structure of the cancellous bone and bone mineral density of SHJH ^hr mice aged 4, 8 and 26 weeks were measured by micro-CT. Histopathological changes of bone and joint of 8-week-old mice were observed. Results Compared with ICR mice, the female and male body mass of SHJH ^hr mice were significantly lower at the age of 16 weeks (P < 0.05), and the reproductive performance of female mice was low (P < 0.01) or did not have normal reproductive capacity. The shortest survival time of SHJH ^hr mice was 57 weeks and the longest was 71 weeks, which was shorter than those of normal ICR mice, showing obvious rapid aging phenomenon. At the same time, some physiological and biochemical indexes of blood and pathological changes of bone and cartilage tissues also showed the accelerated aging and abnormality of animal physiological functions. Conclusion SHJH ^hr mice have some biological characteristics of rapid aging as well as some physiological and pathological changes caused by aging.

Key words: Spontaneous rapid aging, Bio-characteristics, Aging phenotype, SHJH ^hr mice

CLC Number:

Q95-33

Huiqing TANG, Shufu CHANG, Zhifeng YU, Lei ZHANG, Xiaoqian TAN, Wei QU, Liang LI, Zhen QIAN, Jianzhong GU, Ping XU. Investigation on Biological Characteristics and Aging Phenotype of SHJH ^hr Mice[J]. Laboratory Animal and Comparative Medicine, 2023, 43(1): 44-52.

Figures/Tables 9

References 18

1	AUSTAD S N. Diverse aging rates in metazoans: targets for functional genomics[J]. Mech Ageing Dev, 2005, 126(1):43-49. DOI:10.1016/j.mad.2004.09.022 .
2	MARTIN G M. Genetic modulation of senescent phenotypes in Homo sapiens [J]. Cell, 2005, 120(4):523-532. DOI:10.1016/j.cell.2005.01.031 .
3	LI Y C, GAO J F, GUAN Y L,et al. Novel rhino-like SHJH^hr mice with thyroid dysfunction[J]. Zoological Research, 2021, 42(6): 734-738. DOI: 10.24272/j.issn.2095-8137.2021.211
4	LEE Y T, LIN H Y, CHAN Y W F, et al. Mouse models of atherosclerosis: a historical perspective and recent advances[J]. Lipids Health Dis, 2017, 16(1):12. DOI:10.1186/s12944-016-0402-5 .
5	TAKEDA T. Senescence-accelerated mouse (SAM) with special references to neurodegeneration models, SAMP8 and SAMP10 mice[J]. Neurochem Res, 2009, 34(4):639-659. DOI:10.1007/s11064-009-9922-y .
6	YUAN R, TSAIH S W, PETKOVA S B, et al. Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF₁ levels[J]. Aging Cell, 2009, 8(3):277-287. DOI:10.1111/j.1474-9726.2009.00478.x .
7	MORITA D, HIGUCHI Y, MAKIDA K, et al. Effects of ultraviolet irradiation with a LED device on bone metabolism associated with vitamin D deficiency in senescence-accelerated mouse P6[J]. Heliyon, 2020, 6(2): e03499. DOI:10.1016/j.heliyon.2020.e03499 .
8	HASTY P, VIJG J. Accelerating aging by mouse reverse genetics: a rational approach to understanding longevity[J]. Aging Cell, 2004, 3(2):55-65. DOI:10.1111/j.1474-9728. 2004. 00082.x .
9	TAYLOR P N, ALBRECHT D, SCHOLZ A, et al. Global epidemiology of hyperthyroidism and hypothyroidism[J].Nat Rev Endocrinol, 2018, 14(5):301-316. DOI:10.1038/nrendo. 2018.18 .
10	李洪涛, 杜春燕, 王纯耀, 等. 豫医无毛小鼠生殖及乳腺功能观察[J]. 郑州大学学报(医学版), 2003, 38(2):198-199. DOI:10.13705/j.issn.1671-6825.2003.02.020 .
	LI H T, DU C Y, WANG C Y, et al. Study on procreation and mammary gland of Yuyi hairless mice[J]. J Henan Med Univ (Med Sci), 2003, 38(2):198-199. DOI:10.13705/j.issn.1671-6825.2003.02.020 .
11	施新猷, 王四旺, 顾为望, 等. 比较医学[M]. 西安: 陕西科学技术出版社, 2003.
	SHI X, WANG S, GU W, et al. Comparative medicine[M]. Xi'an: Shaanxi Science And Technology Press, 2003.
12	GOODRICK C L. Body weight increment and length of life: the effect of genetic constitution and dietary protein[J]. J Gerontol, 1978, 33(2):184-190. DOI:10.1093/geronj/33.2.184 .
13	FLURKEY K, MCURRER J, HARRISON D. Mouse models in aging research[M]//The mouse in biomedical research. Amsterdam: Elsevier, 2007:637-672. DOI:10.1016/b978-012369454-6/50074-1 .
14	杜春燕, 李洪涛, 章金涛, 等. 豫医无毛小鼠寿命观察[J]. 郑州大学学报(医学版), 2003, 38(2):196-198. DOI:10.13705/j.issn.1671-6825.2003.02.019 .
	DU C Y, LI H T, ZHANG J T, et al. Investigation on life span of Yuyi hairless mice[J]. J Henan Med Univ (Med Sci), 2003, 38(2):196-198. DOI:10.13705/j.issn.1671-6825.2003.02.019 .
15	FLURKEY K, STADECKER M, MILLER R A. Memory T lymphocyte hyporesponsiveness to non-cognate stimuli: a key factor in age-related immunodeficiency[J]. Eur J Immunol, 1992, 22(4):931-935. DOI:10.1002/eji.1830220408 .
16	LERNER A, YAMADA T, MILLER R A. Pgp-1hi T lymphocytes accumulate with age in mice and respond poorly to concanavalin A[J]. Eur J Immunol, 1989, 19(6):977-982. DOI:10.1002/eji.1830190604 .
17	MILLER R A. Immune system [M]. //MASORO EJ. Handbook of physiology, New York: Oxford University Press, 1995:555-590.
18	KIM Y H, PARK M, CHO K A, et al. Tonsil-derived mesenchymal stem cells promote bone mineralization and reduce marrow and visceral adiposity in a mouse model of senile osteoporosis[J]. Stem Cells Dev, 2016, 25(15):1161-1171. DOI:10.1089/scd.2016.0063 .

项目 Item	交配组合 Mating type	第1胎 1st born	第2胎 2nd born	第3胎 3rd born	第4胎 4th born
窝产仔数/只 Litter size, n	对照组（ICR）	15.7±2.4	17.2±1.7	16.8±2.1	15.9±1.9
	hr/hr♂ ×+/hr ♀	16.6±1.9	16.3±2.6	15.8±1.8	16.5±2.2
	+/hr♂ ×hr/hr ♀	14.1±2.1	10.9±1.9^*	8.8±2.9^*	6.1±2.7^**
	hr/hr ♂ ×hr/hr ♀	13.6±2.4	11.5±2.3^*	8.2±3.1^*	7.1±2.8^**
胎间隔 Fetal interval/d	对照组（ICR）	23.4±3.2	28.3±2.7	29.7±2.7	32.2±4.2
	hr/hr♂ ×+/hr ♀	22.9±2.8	30.2±3.1	28.5±4.2	30.9±3.8
	+/hr♂ ×hr/hr ♀	24.5±3.6	42.6±5.7^*	61.1±7.2^**	82.8±35.2^**
	hr/hr♂ ×hr/hr ♀	23.8±3.3	44.2±6.1^*	68.2±12.3^**	87.4±29.9^**
离乳成活率 Survival rate of weaning/%	对照组（ICR）	93.4 (9.34/10)	96.3 (9.63/10)	96.7 (9.67/10)	94.9 (9.49/10)
	hr/hr ♂ ×+/hr ♀	94.2 (9.42/10）	95.6 (9.56/10)	94.8 (9.48/10)	95.1 (9.51/10)
	+/hr♂ ×hr/hr ♀	52.9 (5.29/10)^**	41.2 (4.12/10)^**	32.1 (3.21/10)^**	11.4 (1.14/10)^**
	hr/hr ♂ ×hr/hr ♀	51.4 (5.14/10)^**	42.7 (4.27/10)^**	28.2 (2.82/10)^**	8.7 (0.87/10)^**

项目 Item	交配组合 Mating type	第1胎 1st born	第2胎 2nd born	第3胎 3rd born	第4胎 4th born
窝产仔数/只 Litter size, n	对照组（ICR）	15.7±2.4	17.2±1.7	16.8±2.1	15.9±1.9
	hr/hr♂ ×+/hr ♀	16.6±1.9	16.3±2.6	15.8±1.8	16.5±2.2
	+/hr♂ ×hr/hr ♀	14.1±2.1	10.9±1.9^*	8.8±2.9^*	6.1±2.7^**
	hr/hr ♂ ×hr/hr ♀	13.6±2.4	11.5±2.3^*	8.2±3.1^*	7.1±2.8^**
胎间隔 Fetal interval/d	对照组（ICR）	23.4±3.2	28.3±2.7	29.7±2.7	32.2±4.2
	hr/hr♂ ×+/hr ♀	22.9±2.8	30.2±3.1	28.5±4.2	30.9±3.8
	+/hr♂ ×hr/hr ♀	24.5±3.6	42.6±5.7^*	61.1±7.2^**	82.8±35.2^**
	hr/hr♂ ×hr/hr ♀	23.8±3.3	44.2±6.1^*	68.2±12.3^**	87.4±29.9^**
离乳成活率 Survival rate of weaning/%	对照组（ICR）	93.4 (9.34/10)	96.3 (9.63/10)	96.7 (9.67/10)	94.9 (9.49/10)
	hr/hr ♂ ×+/hr ♀	94.2 (9.42/10）	95.6 (9.56/10)	94.8 (9.48/10)	95.1 (9.51/10)
	+/hr♂ ×hr/hr ♀	52.9 (5.29/10)^**	41.2 (4.12/10)^**	32.1 (3.21/10)^**	11.4 (1.14/10)^**
	hr/hr ♂ ×hr/hr ♀	51.4 (5.14/10)^**	42.7 (4.27/10)^**	28.2 (2.82/10)^**	8.7 (0.87/10)^**

项目 Item	SHJH ^hr 雄鼠 Male SHJH ^hr	ICR 雄鼠 Male ICR	SHJH ^hr 雌鼠 Female SHJH ^hr	ICR 雌鼠 Female ICR
WBC /(10⁹·L^-1)	4.88±1.85	5.80±0.81	5.98±2.64	4.69±1.00
RBC/(10¹²·L^-1)	8.44±0.62	7.78±0.43	8.67±0.61	7.60±0.16
HGB ρ/(g·L^-1)	139.2±6.84	125.5±10.34	147.0±8.29	122.25±1.71
HCT/%	47.64±0.85	41.43±3.20	49.06±1.62	40.33±0.83
MCV/fL	56.68±3.68	53.23±1.37	56.90±4.91	53.08±0.92
MCH m/pg	16.54±0.50	16.12±0.63	16.98±0.51	16.10±0.49
MCHC ρ/(g·L^-1)	292.10±12.77	303.10±4.55	299.90±20.78	303.25±9.54
PLT/(10⁹·L^-1)	1 644.30±131.48	1 526.50±199.58	1 449.60±144.21	1 360.75±81.71
RDW-SD/fL	31.59±2.34	31.67±2.29	32.38±2.03	38.70±2.80
RDW-CV/%	16.86±1.32	17.90±1.72	17.71±1.67	21.51±1.03
PDW/fL	7.18±0.26	7.18±0.32	7.24±0.35	7.20±0.37
MPV/fL	6.91±0.17	7.00±0.24	6.95±0.17	7.11±0.18
P-LCR/%	5.30±0.87	5.80±1.42	5.85±0.87	6.82±0.68
PCT/%	1.14±0.11	1.07±0.11	1.01±0.10	0.97±0.06
NEUT/(10⁹·L^-1)	1.39±0.46	0.97±0.14	2.26±0.87	1.09±0.22
LYMPH/(10⁹·L^-1)	3.38±1.43	4.72±0.71	5.40±2.79	3.50±0.85
MONO/(10⁹·L^-1)	0.03±0.02	0.03±0.01	0.03±0.03	0.01±0.01
EO/(10⁹·L^-1)	0.08±0.04	0.08±0.04	0.28±0.29	0.08±0.03
BASO/(10⁹·L^-1)	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00
NEUT/%	29.01±4.43	16.65±1.64	29.68±8.27	23.75±4.65
LYMPH/%	68.66±4.81	81.25±2.19	66.56±7.93	74.18±4.42
MONO/%	0.52±0.30	0.58±0.17	0.41±0.37	0.33±0.10
EO/%	1.81±0.78	1.42±0.66	3.28±2.08	1.63±0.53
BASO/%	0.00±0.00	0.10±0.10	0.07±0.04	0.13±0.15
RET/(10⁹·L^-1)	584.44±157.99	977.67±140.83^*	662.89±190.72	1 562.98±174.91^*
RET/%	7.05±2.28	12.57±1.73^*	7.78±2.62	20.59±2.59^**
LFR/%	52.63±3.37	51.48±3.75	50.66±2.35	44.86±2.94
MFR/%	16.46±1.19	15.03±2.05	15.20±1.40	14.68±0.32
HFR/%	30.91±3.37	33.50±5.41	34.14±2.78	40.45±3.11
IRF/%	47.37±3.37	48.53±3.75	49.34±2.35	55.13±2.94

项目 Item	SHJH ^hr 雄鼠 Male SHJH ^hr	ICR 雄鼠 Male ICR	SHJH ^hr 雌鼠 Female SHJH ^hr	ICR 雌鼠 Female ICR
WBC /(10⁹·L^-1)	4.88±1.85	5.80±0.81	5.98±2.64	4.69±1.00
RBC/(10¹²·L^-1)	8.44±0.62	7.78±0.43	8.67±0.61	7.60±0.16
HGB ρ/(g·L^-1)	139.2±6.84	125.5±10.34	147.0±8.29	122.25±1.71
HCT/%	47.64±0.85	41.43±3.20	49.06±1.62	40.33±0.83
MCV/fL	56.68±3.68	53.23±1.37	56.90±4.91	53.08±0.92
MCH m/pg	16.54±0.50	16.12±0.63	16.98±0.51	16.10±0.49
MCHC ρ/(g·L^-1)	292.10±12.77	303.10±4.55	299.90±20.78	303.25±9.54
PLT/(10⁹·L^-1)	1 644.30±131.48	1 526.50±199.58	1 449.60±144.21	1 360.75±81.71
RDW-SD/fL	31.59±2.34	31.67±2.29	32.38±2.03	38.70±2.80
RDW-CV/%	16.86±1.32	17.90±1.72	17.71±1.67	21.51±1.03
PDW/fL	7.18±0.26	7.18±0.32	7.24±0.35	7.20±0.37
MPV/fL	6.91±0.17	7.00±0.24	6.95±0.17	7.11±0.18
P-LCR/%	5.30±0.87	5.80±1.42	5.85±0.87	6.82±0.68
PCT/%	1.14±0.11	1.07±0.11	1.01±0.10	0.97±0.06
NEUT/(10⁹·L^-1)	1.39±0.46	0.97±0.14	2.26±0.87	1.09±0.22
LYMPH/(10⁹·L^-1)	3.38±1.43	4.72±0.71	5.40±2.79	3.50±0.85
MONO/(10⁹·L^-1)	0.03±0.02	0.03±0.01	0.03±0.03	0.01±0.01
EO/(10⁹·L^-1)	0.08±0.04	0.08±0.04	0.28±0.29	0.08±0.03
BASO/(10⁹·L^-1)	0.00±0.00	0.00±0.00	0.00±0.00	0.00±0.00
NEUT/%	29.01±4.43	16.65±1.64	29.68±8.27	23.75±4.65
LYMPH/%	68.66±4.81	81.25±2.19	66.56±7.93	74.18±4.42
MONO/%	0.52±0.30	0.58±0.17	0.41±0.37	0.33±0.10
EO/%	1.81±0.78	1.42±0.66	3.28±2.08	1.63±0.53
BASO/%	0.00±0.00	0.10±0.10	0.07±0.04	0.13±0.15
RET/(10⁹·L^-1)	584.44±157.99	977.67±140.83^*	662.89±190.72	1 562.98±174.91^*
RET/%	7.05±2.28	12.57±1.73^*	7.78±2.62	20.59±2.59^**
LFR/%	52.63±3.37	51.48±3.75	50.66±2.35	44.86±2.94
MFR/%	16.46±1.19	15.03±2.05	15.20±1.40	14.68±0.32
HFR/%	30.91±3.37	33.50±5.41	34.14±2.78	40.45±3.11
IRF/%	47.37±3.37	48.53±3.75	49.34±2.35	55.13±2.94

项目Item	SHJH ^hr♂	ICR ♂	SHJH^hr ♀	ICR ♀
GPT z/(U·L^-1)	42.63±7.25	34.53±7.97	40.70±9.36	35.30±4.27
GOT z/(U·L^-1)	135.74±51.87	110.95±32.88	154.69±34.67	109.73±25.97
TP ρ//(g·L^-1)	52.82±1.70	47.48±3.21	52.49±3.35	42.64±1.74
ALB ρ//(g·L^-1)	30.30±1.00	28.20±1.85	31.60±2.30	26.21±0.82
GLOB ρ//(g·L^-1)	22.53±0.97	19.29±1.38	20.89±1.93	16.44±0.95
A/G	1.34±0.05	1.46±0.02	1.52±0.15	1.59±0.05
TBIL c/(µmol·L^-1)	0.98±0.33	1.07±0.40	0.47±0.18^*	1.05±0.24
ALP z/(U·L^-1)	188.18±36.13	199.25±50.96	217.22±48.40	191.63±23.97
GLU c/(mmol·L^-1)	6.62±0.64	6.98±1.35	5.49±0.74	6.45±0.52
Urea c/(mmol·L^-1)	9.38±1.57*	6.36±0.52	9.27±1.16^*	6.24±0.61
Crea c/(µmol·L^-1)	11.39±0.96	11.25±1.89	13.77±1.40	13.12±0.90
UA c/(µmol·L^-1)	129.08±21.23	91.65±4.14	112.01±18.22	91.30±5.86
Ca c/(mmol·L^-1)	2.42±0.07	2.59±0.08	2.38±0.05	2.55±0.07
P c/(mmol·L^-1)	2.84±0.35	3.76±0.25	3.43±0.22	3.78±0.22
CHOl c/(mmol·L^-1)	3.55±0.37	3.15±0.48	1.96±0.33	1.98±0.23
TG c/(mmol·L^-1)	2.22±0.70*	1.34±0.34	1.59±0.37*	0.85±0.31
HDL-C/(mmol·L^-1)	2.11±0.19	2.48±0.40	1.35±0.24	1.54±0.19
LDL-C/(mmol·L^-1)	0.23±0.03	0.40±0.04	0.18±0.03	0.27±0.05
CK z/(U·L^-1)	2 780.68±1 965.23	1 838.40±859.10	2 530.90±897.23	1 906.9±846.35
LDH z/(U·L^-1)	1 063.48±155.12	811.95±208.50	930.97±132.80	610.02±177.99
K c/(mmol·L^-1)	6.56±0.38	6.50±0.42	5.97±0.35	5.87±0.23
Na c/(mmol·L^-1)	168.35±2.34	162.78±3.02	167.10±1.97	159.53±1.41
Cl c/(mmol·L^-1)	116.08±3.16	109.47±1.14	118.26±1.72	109.52±0.87
CHE z/(U·L^-1)	7 596.10±1 065.80	6 658.75±172.88	9 730.10±1 555.38	5 431.25±1 050.21
NEFA c/(mmol·L^-1)	1.42±0.24^*	0.94±0.15	1.11±0.16^**	0.60±0.17