Sociability and preference for social novelty in five inbred strains: an approach to assess autistic‐like behavior in mice

May combine two claims.

Higher numbers of sniffs were directed toward stranger 1 than towards the empty wire cage, and towards the novel stranger 2 vs. the now-familiar stranger 1, in C57BL/6J, DBA/2J and FVB/NJ male mice.

“Higher numbers of sniffs were directed toward stranger 1 than towards the empty wire cage, and towards the novel stranger 2 vs. the now-familiar stranger 1, in C57BL/6J, DBA/2J and FVB/NJ male mice (Nadler et al. 2004).”

• cites Nadler et al. 2004 sourcePartly supported

  The “Social behavior tasks in three inbred strains” section reports that males of all three named strains spent more time sniffing the cage containing stranger 1 than the empty cage, and more time sniffing stranger 2 than stranger 1. The “Sociability test” section specifies that sniffing was scored as cumulative duration in seconds, not as a number of sniffs; that measurement in the claim is unsupported. Page numbers are unavailable in our copy. (LLM, conf=0.86)

  Experimental — accuracy not yet measured

May combine two claims.

General health, neurological reflexes, activity levels, motor functions and sensory abilities were normal in most regards for the strains tested.

“General health, neurological reflexes, activity levels, motor functions and sensory abilities were normal in most regards for the strains tested.”

The quote only partly states this claim.

Young female C57BL/6J mice showed similar levels of sociability to males.

“Similar levels of sociability were clearly evident in a group of young female C57BL/6J mice.”

May combine two claims.

A/J was the only strain tested that failed to spend more time with a conspecific, and spent most of its time in the central chamber after the initial 5-minute habituation session.

“A/J was the only strain tested that failed to spend more time with a conspecific, and spent most of its time in the central chamber after the initial 5-minute habituation session.”

May combine two claims.

All of the inbred strains were able to locate buried food, supporting an interpretation that none were anosmic, which could have severely impacted social behaviors by blocking detection of olfactory cues emitted by the stranger mice.

“All of the inbred strains were able to locate buried food, supporting an interpretation that none were anosmic, which could have severely impacted social behaviors by blocking detection of olfactory cues emitted by the stranger mice.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The majority of the subjects successfully located and retrieved the buried food.

“For the olfactory test, the majority of the subjects successfully located and retrieved the buried food.”

May combine two claims.

The A/J group showed significant increases in time spent in the side regions and in number of entries when the openings between chambers were more accessible.

“As shown in Fig. 9, the A/J group did show significant increases in time spent in the side regions (Fig. 9a, significant main effect of retest, F 1,9 ¼ 11.343, P ¼ 0.0083) and in number of entries (Fig. 9b, significant main effect of retest, F 1,9 ¼ 13.302, P ¼ 0.0053) when the openings between chambers were more accessible.”

May combine two claims.

FVB/NJ strain had significantly higher locomotor scores compared to the other two groups, but this was not reflected in an overall higher number of entries.

“the significantly higher locomotor scores observed in the FVB/NJ strain, in comparison to the other two groups, were not reflected in an overall higher number of entries.”

Probably not a substantial claim: may not pass S3 (load-bearing).

FVB/NJ mice demonstrated a significantly shorter latency for locating the buried food.

“The FVB/NJ mice demonstrated a significantly shorter latency for locating the buried food,”

May combine two claims.

There was a significant interaction between side of chamber and test condition, reflecting preference for the stranger 1 side during the sociability condition and a switch to the stranger 2 side during the social novelty condition.

“A significant interaction was found between side of chamber and test condition (F 1,57 ¼ 67.634, P < 0.0001), reflecting the finding that preference was for the stranger 1 side during the first half of the session (the sociability condition), but switched to the stranger 2 side during the last part of the session (the social novelty condition).”

May combine two claims.

Data from Fig. 8 argue against an artifactual interpretation that hypolocomotion caused the social deficit in the A/J group: repeated testing of A/J in the modified apparatus increased the number of entries but did not yield significant sociability scores.

“Arguing against an artifactual interpretation that hypolocomotion caused the social deficit in the A/J group are the data of Fig. 8. Repeated testing of A/J in the modified apparatus increased the number of entries, but did not yield significant sociability scores.”

May combine two claims.

A/J mice spent significantly more time in the center chamber, indicating a strong preference for the start box not seen in other strains.

“The A/J mice spent significantly more time in the center chamber, indicating a strong preference for the start box that was not seen in the other strains.”

May combine two claims.

In the second group of juvenile C57BL/6J mice, both males and females made equal numbers of entries into each side during the sociability assay, but showed an increased number of entries into the side containing the second novel unfamiliar stranger during the social novelty test.

“In the second group of juvenile C57BL/6J mice, both males and females made equal numbers of entries into each side of the social test box during the assay for sociability, but showed an increased number of entries into the side of the social box containing the second, 'novel' unfamiliar stranger during the test for social novelty.”

May combine two claims.

There were no significant differences between the strains in body weight or rotarod performance.

“There were no significant differences between the strains in body weight or rotarod performance (see Table 1 for mean latency to fall on the second trial).”

May combine two claims.

For juvenile male mice, number of entries did not reflect the trends for social preference seen in the duration measures, and only partially correlated with their locomotor activity independently quantitated in the open field.

“Therefore, for the juvenile male mice, number of entries did not reflect the trends for social preference seen in the duration measures, and only partially correlated with their locomotor activity independently quantitated in the open field.”

May combine two claims.

Low locomotor scores in DBA/2J and high locomotor scores in FVB/NJ appeared unrelated to amount of time spent in the chamber with stranger 1 and stranger 2.

“In addition, low locomotor scores in DBA/2J and high locomotor scores in FVB/NJ appeared to be unrelated to amount of time spent in the chamber with stranger 1 and stranger 2.”

May combine two claims.

Significant preferences for sociability or preference for social novelty were not observed for number of chamber entries in any of the inbred strains.

“Significant preferences for sociability (Fig. 3a) or preference for social novelty (Fig. 3b) were not observed for number of chamber entries in any of the inbred strains.”

Probably not a substantial claim: may not pass S3 (load-bearing).

In the present study, the juvenile male mice made nests and huddled together while sleeping.

“In the present study, the juvenile male mice made nests and huddled together while sleeping.”

Classified as probably not a substantial claim. May combine two claims.

Autistic individuals may avoid unfamiliar social partners and display diminished interest in novelty.

“Autistic individuals may further avoid unfamiliar social partners and display diminished interest in novelty (American Psychiatric Association 1994).”

• cites American Psychiatric Association 1994Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

May combine two claims.

The wire cage modification focuses the task on social approach tendencies relevant to the social approach deficit in autism while avoiding potential confounds from aggressive or sexual interactions.

“This modification focuses the task on social approach tendencies, relevant to the social approach deficit in autism, while avoiding potential confounds resulting from aggressive or sexual interactions.”

• AssumptionRests on an assumption: Most autistic individuals demonstrate reduced or unusual social approach.

Classified as probably not a substantial claim.

A series of independent control experiments was conducted to evaluate potential confounding factors.

“To ensure that differences in social behaviors were not artifacts of other aspects of mouse behaviors, a series of independent control experiments was conducted to evaluate potential confounding factors.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The number of times the mouse exited from the habituated empty central chamber into the novel empty chamber provided a general measure of locomotor function.

“The number of times that the mouse exited from the habituated empty central chamber into the novel empty chamber provided a general measure of locomotor function.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Social behaviors have been explored in mice with mutations in candidate genes such as oxytocin, monoamine oxidase-A, fragile X and dishevelled-1.

“Social behaviors have been explored in mice with mutations in candidate genes such as oxytocin (Winslow & Insel 2002;Young et al. 2002), monoamine oxidase-A (Shih & Chen 1999), fragile X (Churchill et al. 2002;Mineur et al. 2002) and dishevelled-1 (Lijam et al. 1997).”

• cites Winslow & Insel 2002 sourceNot checked — no full text of the source
• cites Young et al. 2002 sourceNot checked — no full text of the source
• cites Shih & Chen 1999Not checked — no full text of the source

Classified as probably not a substantial claim.

Further controls were designed to detect additional symptoms relevant to autism, such as abnormalities in locomotion or motor coordination, that could directly affect performance of the social task.

“Further controls were designed to detect additional symptoms relevant to autism, such as abnormalities in locomotion or motor coordination (Hallett et al. 1993;Piven et al. 1997), that could directly affect performance of the social task.”

• cites Hallett et al. 1993 sourceNot checked — no full text of the source
• cites Piven et al. 1997 sourceNot checked — no full text of the source

Classified as probably not a substantial claim.

Measures of general health, home cage behavior and neurological reflexes were conducted to rule out gross physical abnormalities.

“Measures of general health, home cage behavior and neurological reflexes were conducted to rule out gross physical abnormalities (Crawley 2000).”

• cites Crawley 2000Not checked — no full text of the source

Classified as probably not a substantial claim.

Retrieval of food buried in cage bedding was quantitated in a 15-minute olfactory test to ensure that subject mice were not grossly impaired in olfaction abilities.

“Retrieval of food buried in cage bedding was quantitated in a 15-minute olfactory test, to ensure that the subject mice were not grossly impaired in olfaction abilities.”

Probably not a substantial claim: may not pass S3 (load-bearing).

A large body of evidence from twin and family studies supports the important role of genetic factors in the etiology of autism.

“A large body of evidence from twin and family studies supports the important role of genetic factors in the etiology of autism (Bailey et al. 1995;Ritvo et al. 1989;Szatmari et al. 1998).”

• cites Bailey et al. 1995 sourceNot checked — no full text of the source
• cites Ritvo et al. 1989Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Szatmari et al. 1998 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S4 (based).

The present mouse tasks were designed to maximize face validity to some of the core symptoms of autism.

“The present mouse tasks were designed to maximize face validity to some of the core symptoms of autism.”

Classified as probably not a substantial claim.

A/J mice were given a second test one week later with the dividing walls between the chamber sides partially retracted to facilitate exploration.

“Therefore, the A/J mice were given a second test one week later, with the dividing walls between the chamber sides partially retracted to facilitate exploration.”

Classified as probably not a substantial claim.

Given the primacy of social impairment in autism, the authors considered this symptom to be fundamental to a mouse model of autism.

“Given the primacy of social impairment in autism, we considered this symptom to be fundamental to a mouse model of autism (Insel 2001).”

• cites Insel 2001Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

Classified as probably not a substantial claim.

Several additional behavioral assays were performed in the initial set of juvenile male mice as controls for sensory and motor abilities to ensure that the test mice were physically able to perform the procedures necessary for the social tasks.

“Several additional behavioral assays were performed in the initial set of juvenile male mice (C57BL/6J, DBA/2J and FVB/ NJ).These assays were designed as controls for sensory and motor abilities, etc., to ensure that the test mice were physically able to perform the procedures necessary for the social tasks described above.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

The chambers of the social apparatus were cleaned and fresh paper chip bedding was added between trials.

“The chambers of the social apparatus were cleaned and fresh paper chip bedding was added between trials.”

Probably not a substantial claim: may not pass S3 (load-bearing).

The location of stranger 1 in the left vs right side chamber was systematically alternated between trials.

“The location of stranger 1 in the left vs. right side chamber was systematically alternated between trials.”

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Human observers attain a high level of proficiency after only one or two practice sessions, with high rates (greater than 95%) of interrater reliability between trained observers.

“In our experience to date with the present procedures, human observers attain a high level of proficiency after only one or two practice sessions, with high rates (greater than 95%) of interrater reliability between trained observers.”

Classified as probably not a substantial claim. May combine two claims.

The present protocol used a small wire cage to enclose the stimulus mouse, which allowed visual, auditory and olfactory contact between the mice, but prevented the occurrence of aggressive and other responses.

“The present protocol used a small wire cage to enclose the stimulus mouse, which allowed visual, auditory and olfactory contact between the mice, but prevented the occurrence of aggressive and other responses.”

May combine two claims.

From an early age, autistic children show low levels of eye contact and affective responses, less orientation toward others and language deficits, with a concomitant paucity of speech and social communication.

“From an early age, autistic children show low levels of eye contact and affective responses, less orientation toward others and language deficits, with a concomitant paucity of speech and social communication (for review, see Tager-Flusberg et al. 2001).”

• cites Tager-Flusberg et al. 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The stranger mouse was enclosed in a small round wire cage that allowed nose contact between bars but prevented fighting.

“The stranger mouse was enclosed in a small, round wire cage (Galaxy Cup, Spectrum Diversified Designs, Inc., Streetsboro, OH), which allowed nose contact between the bars, but prevented fighting.”

May combine two claims.

Previous work in social recognition has shown that mice show both habituation of olfactory responses directed toward an unfamiliar conspecific, and dishabituation, with a reinstatement of social sniffing, when a novel stimulus animal is presented.

“Previous work in social recognition has shown that mice show both habituation of olfactory responses directed toward an unfamiliar conspecific, and dishabituation, with a reinstatement of social sniffing, when a novel stimulus animal is presented (Bluthe et al. 1993;Dluzen & Kreutzberg 1993;Ferguson et al. 2000;Kogan et al. 2000;Winslow & Camacho 1995).”

• cites Bluthe et al. 1993 sourceNot checked — no full text of the source
• cites Dluzen & Kreutzberg 1993 sourceNot checked — no full text of the source
• cites Ferguson et al. 2000 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Alternatively, the A/J data may reflect low levels of open field exploratory behaviors and high levels of anxiety-like behaviors reported for A/J mice in other studies, and reflected in the low number of entries in the present study.

“Alternatively, these data may reflect the low levels of open field exploratory behaviors and high levels of anxiety-like behaviors in the light/dark transitions test reported for A/J mice in other studies (Bouwknecht & Paylor 2002;Mathis et al. 1994Mathis et al. , 1995;;Thifault et al. 2002;Wahlsten et al. 2003) and reflected in the low number of entries in the present study.”

• cites Bouwknecht & Paylor 2002 sourceNot checked — no full text of the source
• cites Mathis et al. 1994 sourceNot checked — no full text of the source
• cites Thifault et al. 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing), S4 (based). May combine two claims.

The present procedures for the sociability and social novelty tests are designed to be simple, quantitative and easily mastered by investigators.

“The present procedures for the sociability and social novelty tests are designed to be simple, quantitative and easily mastered by investigators.”

Classified as probably not a substantial claim.

The present methods were designed to quantitate levels of sociability and preference for social novelty using a simple scoring approach for laboratory mice.

“Therefore, the present methods were designed to quantitate levels of sociability, i.e. tendency to initiate social contact, and preference for social novelty, i.e. tendency to initiate social contacts with a new individual as compared to someone familiar from past experience, using a simple scoring approach for laboratory mice.”

Probably not a substantial claim: may not pass S3 (load-bearing).

Some autistic patients demonstrate aberrant motor responses, including repeated hand flapping, jumping and other repetitive and stereotyped behaviors.

“For example, some autistic patients demonstrate aberrant motor responses, including repeated hand flapping, jumping and other repetitive and stereotyped behaviors (Bodfish et al. 2000;Tager-Flusberg et al. 2001).”

• cites Bodfish et al. 2000 sourceNot checked — no full text of the source
• cites Tager-Flusberg et al. 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Altered sensory responses have been reported, including both hypo- and hyper-reactivity to environmental stimuli.

“Altered sensory responses have been reported, including both hypo-and hyper-reactivity to environmental stimuli (Baranek 2002).”

• cites Baranek 2002 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Observational findings in some of these behavioral domains have been reported in some targeted gene mutations, e.g. deficits in social interaction within the home cage have been reported for mice deficient in the dishevelled-1 gene or the NMDA NR1 subunit.

“Observational findings in some of these behavioral domains have been reported in some targeted gene mutations, e.g.deficits in social interaction within the home cage have been reported for mice deficient in the dishevelled-1 gene (Lijam et al. 1997) or the NMDA NR1 subunit (Mohn et al. 1999).”

• cites Lijam et al. 1997 sourceNot checked — no full text of the source
• cites Mohn et al. 1999 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Use of the three-chambered apparatus for demonstrating social preference was adapted by Brodkin et al. (2004) to investigate social approach and avoidance in female mice.

“Use of the three-chambered apparatus for demonstrating social preference (Insel 2001) was adapted by Brodkin et al. (2004) to investigate social approach and avoidance in female mice.”

• cites Insel 2001Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Brodkin et al. 2004 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

Observations of mice in these settings have shown that exposure to an unfamiliar stranger typically evokes a period of intense social sniffing, which may be followed by escalating aggressive responses or sexual behavior, dependent upon such factors as age and sex of the unfamiliar conspecific.

“Observations of mice in these settings have shown that exposure to an unfamiliar stranger typically evokes a period of intense social sniffing, which may be followed by escalating aggressive responses or sexual behavior, dependent upon such factors as age and sex of the unfamiliar conspecific (Bluthe et al. 1993;Kogan et al. 2000;Winslow & Camacho 1995).”

• cites Bluthe et al. 1993 sourceNot checked — no full text of the source
• cites Kogan et al. 2000 sourceNot checked — no full text of the source
• cites Winslow & Camacho 1995 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

The mouse model of fragile X syndrome has been characterized by changes in activity and reactivity to acoustic stimuli.

“and the mouse model of fragile X syndrome has been characterized by changes in activity (Bakker et al. 1994;Peier et al. 2000) and reactivity to acoustic stimuli (Chen & Toth 2001;Nielson et al. 2002).”

• cites Bakker et al. 1994Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Peier et al. 2000Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Chen & Toth 2001 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Children with fragile X syndrome often show autistic behavior.

“Children with fragile X syndrome often show autistic behavior (Hagerman et al. 1986),”

• cites Hagerman et al. 1986 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

As noted by Winslow (2003), the analysis of the full behavioral series that can occur in social tests demands familiarity with the mouse ethogram, extensive training and the ability to discern the sometimes rapid and fleeting responses that mice can emit.

“As noted by Winslow (2003), the analysis of the full behavioral series that can occur in social tests demands familiarity with the mouse ethogram, extensive training and the ability to discern the sometimes rapid and fleeting responses that mice can emit.”

• cites Winslow 2003 sourceNot checked — no full text of the source

Probably not a substantial claim: may not pass S3 (load-bearing).

Methods are based on procedures examining pair-bonding in voles and other tests for social behavior in rodents.

“Methods are based on procedures examining pair-bonding in voles (Dean, S.M. & Vandenbergh, J.G. as above), as well as many other elegant tests for social behavior in rodents (Bluthe et al. 1993;Carter et al. 1995;Dluzen & Kreutzberg 1993;Gheusi et al. 1994;Insel and Young 2001;Kogan et al. 2000;Winslow & Camacho 1995;Winslow 2003).”

• cites Bluthe et al. 1993 sourceNot checked — no full text of the source
• cites Carter et al. 1995Not matched

  Couldn’t be matched to a paper in Crossref, so it can’t be checked.

• cites Dluzen & Kreutzberg 1993 sourceNot checked — no full text of the source