Name: FVB-hHTT Q150 KI Mouse
Brand: サイヤジェン（Cyagen）
SKU: C001874

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FVB-hHTT Q150 KI Mouse

製品名

FVB-hHTT Q150 KI Mouse

製品ID

C001874

系統名

FVB/NJCya-Htt^{em1(hHTT*Q150)}/Cya

背景情報

FVB/NJCya

状況

このマウス系統を論文で使用する場合は、「FVB-hHTT Q150 KI Mouse（カタログ番号C001874）はサイアジェンから購入しました。」と引用してください。

Other Target Humanized Mouse Models

Disease Animal Models

Neurodegenerative Diseases

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年齢

遺伝子型

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Other Target Humanized Mouse Models

Disease Animal Models

Neurodegenerative Diseases

基本情報

検証 Data

系統詳細

Huntingtin (HTT) is a disease-associated gene widely expressed in various tissues and organs, including the central nervous system, and is essential for normal development. The coding region of the HTT gene contains a polymorphic trinucleotide (cytosine-adenine-guanine, CAG) repeat sequence near its 5' end, which forms a polyglutamine (polyQ) tract during translation. Huntington's disease is a neurodegenerative disorder characterized by the loss of striatal neurons, caused by the aberrant expression of the CAG repeat sequence in the HTT gene. When the CAG repeat is expanded beyond 35 copies, it leads to abnormal polyQ expansion, resulting in incorrect folding of HTT protein fragments, dysregulation of protein-protein interactions, and accumulation in the cell nucleus and neuronal terminals, ultimately affecting neural signaling, intracellular protein transport, and mitochondrial function^[1]. Currently, there are no effective drugs or methods to prevent or treat Huntington's disease, and there is a great need for further research into its mechanisms and the development of therapeutic approaches^[2].

This strain is an hHTT Q150 knock-in mouse model generated by gene editing technology, in which a mutated human HTT gene sequence carrying 150 CAG repeats is inserted into the mouse genome. Literature reports have shown that these mice exhibit pathological features and functional impairments characteristic of Huntington's disease, and are suitable for developing and screening therapeutic drugs for Huntington's disease and safety evaluation^[3]. The heterozygous FVB-hHTT Q150 KI mice are viable and fertile.

参考文献

Walker FO. Huntington's disease. Lancet. 2007 Jan 20;369(9557):218-28.

McColgan P, Tabrizi SJ. Huntington's disease: a clinical review. Eur J Neurol. 2018 Jan;25(1):24-34.

Crook ZR, Housman D. Huntington's disease: can mice lead the way to treatment? Neuron. 2011 Feb 10;69(3):423-35.

系統作製戦略

A mutated human HTT gene sequence carrying 150 CAG repeats was knocked into the mouse Htt gene Exon 1.

Figure 1. Gene editing strategy of FVB-hHTT Q150 KI mice.

適用分野

Development and screening of therapeutic drugs for Huntington's disease;

Evaluation of therapeutic drug efficacy and safety for Huntington's disease;

Research on the pathogenesis of Huntington's disease.

検証 Data

1. Gene Expression

Figure 2. Detection of gene expression in the cerebellum, cerebral cortex, hippocampus, and striatum of FVB-hHTT Q150 KI mice and wild-type (WT) mice (8-week-old, heterozygous, female, n=3). RT-qPCR results showed that after humanization of exon 1, the RNA transcription of the murine Htt (mHtt) gene showed a relatively obvious downward trend in the cerebellum and cerebral cortex; however, no significant changes were observed in the hippocampus and striatum. (Data are presented as Mean ± SD)

2. Behavioral Testing: Grip Strength Test

（1）2-month-old

Indications:

No significant alterations in force across all models.

Figure 3. The force for WT and FVB-hHTT Q150 KI mice in the grip strength test. Data were analyzed using unpaired t-test; "ns" indicates no significant differences.

（2）3-month-old

Indications:

No significant alterations in force across all models.

Figure 4. The force for WT and FVB-hHTT Q150 KI mice in the grip strength test. Data were analyzed using unpaired t-test; "ns" indicates no significant differences.

（3）6-month-old

Indications:

Compared to WT mice, male FVB-hHTT Q150 KI exhibited a significant reduction in grip force, suggesting muscle function impairments. In contrast, female and mixed-sex FVB-hHTT Q150 KI showed no significant changes.

Figure 5. Grip strength measurements of FVB-hHTT Q150 KI mice at six months of age. Statistical comparisons were performed using either an unpaired t-test or Welch’s t-test, depending on variance equality. “ns” indicates no statistically significant difference; *p < 0.05.

3. Behavioral Testing: Open Field Test

（1）2-month-old: Travel Distance & Central Area Time Ratio

Indications:

(A-C) No significant alterations in travel distance across all models.

(D-F) For female and sex-mixed comparisons, FVB-hHTT Q150 KI exhibited a significant rise in the central time ratio. This may suggest increased activity levels in HTT mice compared to WT controls, as similar behavioral patterns have been documented in other Cyagen mouse models of hyperactivity. It could also imply that the HTT mice are experiencing cognitive impairment, given that spatial differentiation is a component of cognitive functions, and mice typically avoid traveling in the central area of the open field arena, which is reflected in the WT control behavioral pattern. Both types of abnormalities (hyperactivity and cognitive impairments) have been noted in previous studies on HTT mouse models (Shenoy et al., 2022)^[4].

Figure 6. The travel distance (A-C) and central area time ratio (D-F) for WT and FVB-hHTT Q150 KI mice in open field test. Data were analyzed using unpaired t-test; "ns" indicates no significant differences, **p < 0.01, ***p < 0.001.

（2）2-month-old: Central Speed & Peripheral Speed

Indications:

(A-C) No significant alterations in central speed across all models.

(D-F) No significant alterations in peripheral speed across all models.

Figure 7. The central speed (A-C) and peripheral speed (D-F) for WT and FVB-hHTT Q150 KI mice in the open field test. Data were analyzed using unpaired t-test; "ns" indicates no significant differences.

（3）3-month-old: Travel Distance & Central Area Time Ratio

Indications:

(A-C) No significant alterations in travel distance across all models.

Figure 8. The travel distance (A-C) and central area time ratio (D-F) for WT and FVB-hHTT Q150 KI mice in open field test. Data were analyzed using unpaired t-test; "ns" indicates no significant differences, **p < 0.01, ***p < 0.001.

（4）3-month-old: Central Speed & Peripheral Speed

Indications:

(A-C) For the female comparison, FVB-hHTT Q150 KI exhibited a significant decrease in central speed.

(D-F) For the sex-mixed comparison, FVB-hHTT Q150 KI exhibited a significant decrease in peripheral speed.

Figure 9. The central speed (A-C) and peripheral speed (D-F) for WT and FVB-hHTT Q150 KI mice in the open field test. Data were analyzed using unpaired t-test; "ns" indicates no significant differences.

（5）6-month-old: Travel Distance & Central Area Time Ratio

Indications:

(A~C): In both male and mixed-sex groups, FVB-hHTT Q150 KI mice exhibited a clear decreasing trend in travel distance, suggesting impaired spontaneous locomotor activity.

(D~F): Compared to WT mice, FVB-hHTT Q150 KI mice showed a significant reduction in the central time ratio across sexes, indicative of anxiety-like behavior.

Figure 10. The travel distance (A-C) and central area time ratio (D-F) for WT and FVB-hHTT Q150 KI mice in open field test. (A~C): Travel distance of FVB-hHTT Q150 KI mice in the open field test measured over 10 minutes. Statistical comparisons were conducted using unpaired t-test; "ns" indicates no significant differences, *p<0.05. (D~F): Time ratio spent in the central area of the open field arena (central area time/total time) for FVB-hHTT Q150 KI mice at six months of age, measured over 10 minutes. Statistical comparisons were conducted using unpaired t-test; *p<0.05.

（6）6-month-old: Central Speed & Peripheral Speed

Indications:

No significant differences in movement speed were observed between FVB-hHTT Q150 KI and WT mice.

Figure 11. The central speed (A-C) and peripheral speed (D-F) for WT and FVB-hHTT Q150 KI mice in the open field test. (A~C): Central speed (mm/s) of FVB-hHTT Q150 KI mice at six months of age measured over 10 minutes in the open field arena. Statistical comparisons were conducted using unpaired t-test; "ns" indicates no significant differences. (D~F): Peripheral speed (mm/s) of FVB-hHTT Q150 KI mice at six months of age measured over 10 minutes in the open field arena. Statistical comparisons were conducted using unpaired t-test; "ns" indicates no significant differences, *p<0.05.

4. Behavioral Testing: Rotarod Test

（1）3-month-old

Indications:

Compared to WT, FVB-hHTT Q150 KI showed a significant decrease in latency, regardless of sex or sex-mixed comparisons, indicating impairments in locomotor activity and coordination.

Figure 12. The latency for WT and FVB-hHTT Q150 KI mice in rotarod test. Data were analyzed using unpaired t-test; "ns" indicates no significant differences, **p < 0.01, ***p < 0.001, ****p < 0.0001.

（2）6-month-old

Indications:

FVB-hHTT Q150 KI demonstrated a significant decrease in latency to fall compared to WT mice, regardless of sex or mixed-sex comparisons, indicating deficits in locomotor activity and coordination.

Figure 13. Latency to fall in FVB-hHTT Q150 KI mice at six months of age during the rotarod test. Statistical comparisons were performed using either an unpaired t-test or Welch’s t-test, depending on variance equality. “ns” indicates no statistically significant difference; **p < 0.01, ****p < 0.0001.

5. Grip strength, rotarod, and open field test (14-month-old)

Compared to WT mice, both male and female FVB-hHTT Q150 KI mice exhibited decreased grip strength and reduced latency on the rotarod, indicating impaired locomotor activity and coordination.

Additionally, the reduction in distance traveled and the percentage of time spent in the center further confirm deficits in locomotor activity and an increase in anxiety levels.

Figure 14. The grip strength, rotarod, and open field analysis of FVB-hHTT Q150 KI mice at 14 months.

FVB-hHTT Q150 KI Mouse

基本情報

検証 Data

関連リソース

遺伝子名

遺伝子別名

NCBI ID

染色体

MGI ID

さらに

データシート

系統詳細

参考文献

系統作製戦略

適用分野

1. Gene Expression

2. Behavioral Testing: Grip Strength Test

3. Behavioral Testing: Open Field Test

4. Behavioral Testing: Rotarod Test

5. Grip strength, rotarod, and open field test (14-month-old)

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